Polycystic kidney disease natural history: Difference between revisions

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{{Polycystic kidney disease}}
{{Polycystic kidney disease}}
{{CMG}} {{AE}} [[User:Sergekorjian|Serge Korjian]], [[User:YazanDaaboul|Yazan Daaboul]]
{{CMG}}; {{AE}}{{MKA}}, [[User:Sergekorjian|Serge Korjian]], [[User:YazanDaaboul|Yazan Daaboul]]


==Overview==
==Overview==
The earliest clinical signs of disease in patients with ADPKD include impaired renal concentrating capacity and hypertension. Other signs include flank pain, nephrolithiasis and urinary tract infections. In general half of the patients diagnosed with ADPKD will progress to ESRD by age 60. PDK1 mutants usually progress faster than PDK2 mutants. Factors associated with worse renal outcome include early age at diagnosis, male gender, uncontrolled hypertension, left ventricular hypertrophy, and cystic liver. Extra-renal manifestations in ADPKD include hepatic cysts usually more prevalent in women and with advancing age and declining renal function. Cysts can also be seen in the seminal vesicles, pancreas, and arachnoid membrane. Furthermore, the development of intracranial aneurysms can be a lethal complication in ADPKD patients whose risk is closely linked to the family history of aneurysms. Mitral valve prolapse is also a common cardiac manifestation seen in 25% of patients.
The earliest clinical signs of disease in patients with ADPKD include impaired [[renal]] concentrating capacity and [[hypertension]]. Other signs include [[flank pain]], [[nephrolithiasis]] and [[urinary tract infections]]. In general half of the patients diagnosed with ADPKD will progress to [[ESRD]] by age 60. [[PDK1]] [[mutants]] usually progress faster than [[PDK2]] [[mutants]]. Factors associated with worse [[renal]] outcome include early age at [[diagnosis]], male gender, uncontrolled hypertension, [[left ventricular hypertrophy]], and [[Liver mass|cystic liver]]. Extra-renal manifestations in ADPKD include [[hepatic cysts]] usually more prevalent in women and with advancing age and declining [[renal function]]. [[Cysts]] can also be seen in the [[seminal vesicles]], [[pancreas]], and [[arachnoid membrane]]. Furthermore, the development of [[intracranial aneurysms]] can be a lethal complication in ADPKD patients whose risk is closely linked to the family history of [[aneurysms]]. [[Mitral valve prolapse]] is also a common [[cardiac]] manifestation seen in 25% of patients. Most cases of ARPKD present in the [[neonatal]] period with some disease findings detected on [[prenatal]] [[ultrasound]]. Most feared and common complication of ARPKD is [[pulmonary]] [[hypoplasia]]. Half of ARPKD patients usually progress to [[ESRD]] by age of 10. The prognosis of ARPKD improves in patients who survive the first few months of life. Survival at 15 years for patients of ARPKD ranges from 50% - 80%.


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
===Renal Manifestations: Natural History, Complications, and Prognosis===
===Natural History===
* The earliest detectable functional aberration seen in patients with ADPKD is impaired concentrating capacity with a suboptimal increase in urinary osmolality following water deprivation.<ref name="pmid2709672">{{cite journal| author=Gabow PA, Kaehny WD, Johnson AM, Duley IT, Manco-Johnson M, Lezotte DC et al.| title=The clinical utility of renal concentrating capacity in polycystic kidney disease. | journal=Kidney Int | year= 1989 | volume= 35 | issue= 2 | pages= 675-80 | pmid=2709672 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2709672 }} </ref>
Autosomal dominant polycystic kidney disease (ADPKD):
* The second early manifestation of disease is hypertension. Up to 75% of patients with ADPKD on imaging without any renal insufficiency are hypertensive.<ref name="pmid2239929">{{cite journal| author=Gabow PA| title=Autosomal dominant polycystic kidney disease--more than a renal disease. | journal=Am J Kidney Dis | year= 1990 | volume= 16 | issue= 5 | pages= 403-13 | pmid=2239929 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2239929 }} </ref> Even in young patients, 50% of those aged 20-34 years are hypertensive despite normal renal function.<ref name="pmid15533729">{{cite journal| author=Kelleher CL, McFann KK, Johnson AM, Schrier RW| title=Characteristics of hypertension in young adults with autosomal dominant polycystic kidney disease compared with the general U.S. population. | journal=Am J Hypertens | year= 2004 | volume= 17 | issue= 11 Pt 1 | pages= 1029-34 | pmid=15533729 | doi=10.1016/j.amjhyper.2004.06.020 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15533729 }} </ref>  This is likely to be linked to an increase in the activity of the renin-angiotensin-aldosterone system (RAAS). RAAS overactivity is due to the increase in renin release secondary to renal ischemia brought on by cystic expansion and stretching of renal arterioles. This is further emphasized by the fact that patients with ADPKD generally respond better to ACE inhibitors and angiotensin receptor blockers than patients with essential hypertension.<ref name="pmid2215576">{{cite journal| author=Chapman AB, Johnson A, Gabow PA, Schrier RW| title=The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease. | journal=N Engl J Med | year= 1990 | volume= 323 | issue= 16 | pages= 1091-6 | pmid=2215576 | doi=10.1056/NEJM199010183231602 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2215576 }} </ref>
*The earliest detectable functional aberration seen in patients with ADPKD is impaired concentrating capacity with a suboptimal increase in urinary [[osmolality]] following water deprivation.<ref name="pmid2709672">{{cite journal| author=Gabow PA, Kaehny WD, Johnson AM, Duley IT, Manco-Johnson M, Lezotte DC et al.| title=The clinical utility of renal concentrating capacity in polycystic kidney disease. | journal=Kidney Int | year= 1989 | volume= 35 | issue= 2 | pages= 675-80 | pmid=2709672 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2709672 }} </ref>
* Overt clinical signs and symptoms of renal disease usually appear during the fourth or fifth decade.<ref name="pmid8198379">{{cite journal| author=Fick GM, Gabow PA| title=Natural history of autosomal dominant polycystic kidney disease. | journal=Annu Rev Med | year= 1994 | volume= 45 | issue= | pages= 23-9 | pmid=8198379 | doi=10.1146/annurev.med.45.1.23 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8198379 }} </ref>
*The second early manifestation of disease is [[hypertension]]. Up to 75% of patients with ADPKD on imaging without any [[renal insufficiency]] are [[Hypertension|hypertensive]].<ref name="pmid2239929">{{cite journal| author=Gabow PA| title=Autosomal dominant polycystic kidney disease--more than a renal disease. | journal=Am J Kidney Dis | year= 1990 | volume= 16 | issue= 5 | pages= 403-13 | pmid=2239929 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2239929 }} </ref>
* Approximately 60% of patients suffer from flank pain often requiring cyst decompression surgery. Expanding cysts can often by complicated by hemorrhage that self-resolves but usually causes significant pain.<ref name="pmid8198379">{{cite journal| author=Fick GM, Gabow PA| title=Natural history of autosomal dominant polycystic kidney disease. | journal=Annu Rev Med | year= 1994 | volume= 45 | issue= | pages= 23-9 | pmid=8198379 | doi=10.1146/annurev.med.45.1.23 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8198379 }} </ref>
*Even in young patients, 50% of those aged 20-34 years are [[hypertensive]] despite normal [[renal function]].<ref name="pmid15533729">{{cite journal| author=Kelleher CL, McFann KK, Johnson AM, Schrier RW| title=Characteristics of hypertension in young adults with autosomal dominant polycystic kidney disease compared with the general U.S. population. | journal=Am J Hypertens | year= 2004 | volume= 17 | issue= 11 Pt 1 | pages= 1029-34 | pmid=15533729 | doi=10.1016/j.amjhyper.2004.06.020 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15533729 }} </ref>
* Urinary tract infections occur in up to 70% of patients particularly with gram negative bacteria. Ascending infection can lead to pyelonephritis or cyst infection which are often difficult to differentiate.<ref name="pmid3565428">{{cite journal| author=Schwab SJ, Bander SJ, Klahr S| title=Renal infection in autosomal dominant polycystic kidney disease. | journal=Am J Med | year= 1987 | volume= 82 | issue= 4 | pages= 714-8 | pmid=3565428 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3565428 }} </ref>
*Overt clinical signs and symptoms of [[renal disease]] usually appear during the fourth or fifth decade.<ref name="pmid8198379">{{cite journal| author=Fick GM, Gabow PA| title=Natural history of autosomal dominant polycystic kidney disease. | journal=Annu Rev Med | year= 1994 | volume= 45 | issue= | pages= 23-9 | pmid=8198379 | doi=10.1146/annurev.med.45.1.23 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8198379 }} </ref>
* Nephrolithiasis is also very common due to the distorted urinary system. Approximately 35% of patients will have some form or renal stones.<ref name="pmid8198379">{{cite journal| author=Fick GM, Gabow PA| title=Natural history of autosomal dominant polycystic kidney disease. | journal=Annu Rev Med | year= 1994 | volume= 45 | issue= | pages= 23-9 | pmid=8198379 | doi=10.1146/annurev.med.45.1.23 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8198379 }} </ref>
* Hematuria can be seen in ADPKD especially in advanced cases; however, overt proteinuria is usually uncommon in the context of ADPKD, and proteinuria > 1 g/day should prompt the consideration of a second disease process.<ref name="pmid1496966">{{cite journal| author=Gabow PA, Duley I, Johnson AM| title=Clinical profiles of gross hematuria in autosomal dominant polycystic kidney disease. | journal=Am J Kidney Dis | year= 1992 | volume= 20 | issue= 2 | pages= 140-3 | pmid=1496966 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1496966 }} </ref><ref name="pmid8198379">{{cite journal| author=Fick GM, Gabow PA| title=Natural history of autosomal dominant polycystic kidney disease. | journal=Annu Rev Med | year= 1994 | volume= 45 | issue= | pages= 23-9 | pmid=8198379 | doi=10.1146/annurev.med.45.1.23 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8198379 }} </ref>
* Generally, PKD1 mutants have more severe renal disease with mean age at onset of ESRD around 50 years compared to 75 years in PKD2 mutants. But, regardless of the mutation, 50% of ADPKD patients will reach ESRD by age 60 years.<ref name="pmid10023895">{{cite journal| author=Hateboer N, v Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL et al.| title=Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. | journal=Lancet | year= 1999 | volume= 353 | issue= 9147 | pages= 103-7 | pmid=10023895 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10023895 }} </ref>
* Several factors have been linked to a worse renal outcome (renal function for given age) including early age at diagnosis, male gender, uncontrolled hypertension, left ventricular hypertrophy, cystic liver, gross hematuria, larger kidney volume, and urinary tract infections.<ref name="pmid1614046">{{cite journal| author=Gabow PA, Johnson AM, Kaehny WD, Kimberling WJ, Lezotte DC, Duley IT et al.| title=Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. | journal=Kidney Int | year= 1992 | volume= 41 | issue= 5 | pages= 1311-9 | pmid=1614046 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1614046 }} </ref>


===Extra-renal Manifestations: Natural History, Complications, and Prognosis===
Autosomal recessive polycystic kidney disease (ARPKD):
* The most common extra-renal manifestation of ADPKD is hepatic cysts. It occurs in both ADPKD1 and ADPKD2 and is rarely seen in young children. Classically, the frequency of liver cysts increases with age and declining renal function.<ref name="pmid2365280‎">{{cite journal| author=Gabow PA, Johnson AM, Kaehny WD, Manco-Johnson ML, Duley IT, Everson GT| title=Risk factors for the development of hepatic cysts in autosomal dominant polycystic kidney disease. | journal=Hepatology | year= 1990 | volume= 11 | issue= 6 | pages= 1033-7 | pmid=2365280‎ | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2365280 }} </ref> The CRISP trial showed that approximately 60% of patients between 15 and 24 years of age have documented hepatic cysts on MRI compared to 95% of patients between the ages of 35 and 46.<ref name="pmid17699192‎">{{cite journal| author=Bae KT, Zhu F, Chapman AB, Torres VE, Grantham JJ, Guay-Woodford LM et al.| title=Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort. | journal=Clin J Am Soc Nephrol | year= 2006 | volume= 1 | issue= 1 | pages= 64-9 | pmid=17699192‎ | doi=10.2215/CJN.00080605 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699192 }} </ref> Hepatic cysts are also more common and larger in women. This can be explained by the expression of estrogen receptors on the epithelial lining hepatic cysts. Clinically, evidence that estrogen increases hepatic cyst size and number is apparent in women with ADPKD and multiple pregnancies or on oral contraceptive pills that have a higher prevalence of liver cysts than their age matched controls.<ref name="pmid2365280‎">{{cite journal| author=Gabow PA, Johnson AM, Kaehny WD, Manco-Johnson ML, Duley IT, Everson GT| title=Risk factors for the development of hepatic cysts in autosomal dominant polycystic kidney disease. | journal=Hepatology | year= 1990 | volume= 11 | issue= 6 | pages= 1033-7 | pmid=2365280‎ | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2365280 }} </ref> Liver disease in ADPKD is commonly asymptomatic, but symptoms related to mass-effect such as dyspnea and early satiety, hepatic venous and biliary obstruction. Pain is rare but can be associated cyst hemorrhage, infection, or torsion.<ref name="pmid17434405">{{cite journal| author=Torres VE, Harris PC, Pirson Y| title=Autosomal dominant polycystic kidney disease. | journal=Lancet | year= 2007 | volume= 369 | issue= 9569 | pages= 1287-301 | pmid=17434405 | doi=10.1016/S0140-6736(07)60601-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17434405 }} </ref>
* Most affected individuals present in the [[neonatal]] period with some disease findings detected in [[prenatal]] [[obstetric]] [[ultrasounds]].<ref name="pmid16767405">{{cite journal| author=Sweeney WE, Avner ED| title=Molecular and cellular pathophysiology of autosomal recessive polycystic kidney disease (ARPKD). | journal=Cell Tissue Res | year= 2006 | volume= 326 | issue= 3 | pages= 671-85 | pmid=16767405 | doi=10.1007/s00441-006-0226-0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16767405  }}</ref>
* Cysts can also be found in other organs including the seminal vesicles (40% of men), pancreas (5%), and arachnoid membrane (8%). These are usually asymptomatic but rare cases of recurrent pancreatitis and increased risk of subdural hemorrhage have been reported. <ref name="pmid17434405">{{cite journal| author=Torres VE, Harris PC, Pirson Y| title=Autosomal dominant polycystic kidney disease. | journal=Lancet | year= 2007 | volume= 369 | issue= 9569 | pages= 1287-301 | pmid=17434405 | doi=10.1016/S0140-6736(07)60601-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17434405 }} </ref>
* The most common initial findings in ARPKD patients involve abnormal renal structure and function.<ref name="pmid9587064">{{cite journal| author=Zerres K, Rudnik-Schöneborn S, Steinkamm C, Becker J, Mücher G| title=Autosomal recessive polycystic kidney disease. | journal=J Mol Med (Berl) | year= 1998 | volume= 76 | issue= 5 | pages= 303-9 | pmid=9587064 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9587064  }}</ref>
* One of the most serious extra-renal manifestations is vascular defects including intracranial aneurysms, aortic aneurysms and dissections, and coronary artery aneurysms directly related to polycystins (protein products of PKD1 and 2) expresses on the surface of vascular smooth muscle cells.<ref name="pmid11134244‎">{{cite journal| author=Torres VE, Cai Y, Chen X, Wu GQ, Geng L, Cleghorn KA et al.| title=Vascular expression of polycystin-2. | journal=J Am Soc Nephrol | year= 2001 | volume= 12 | issue= 1 | pages= 1-9 | pmid=11134244‎ | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11134244 }} </ref> Family history is essential in the risk stratification for intracranial aneurysm formation. Intracranial aneurysms can be seen in 6% of patients with no family history of aneurysms compared to 16% of patients with a positive family history.<ref name="pmid11752048">{{cite journal| author=Pirson Y, Chauveau D, Torres V| title=Management of cerebral aneurysms in autosomal dominant polycystic kidney disease. | journal=J Am Soc Nephrol | year= 2002 | volume= 13 | issue= 1 | pages= 269-76 | pmid=11752048 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11752048 }} </ref> The aneurysms are usually asymptomatic and the mean age at rupture is at 39 years, 12 years younger than in the general population.<ref name="pmid17434405">{{cite journal| author=Torres VE, Harris PC, Pirson Y| title=Autosomal dominant polycystic kidney disease. | journal=Lancet | year= 2007 | volume= 369 | issue= 9569 | pages= 1287-301 | pmid=17434405 | doi=10.1016/S0140-6736(07)60601-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17434405 }} </ref>
* Approximately 30% of patients have no lab abnormalities at presentation.
* Mitral valve prolapse is also a common extra-renal manifestation seen in approximately 25% of ADPKD patients on echocardiography. Aortic regurgitation can occur in association with ascending aortic aneurysms. Valvular disease is often asympmtomatic in ADPKD patients and very rarely requires valve replacement.<ref name="pmid3419455">{{cite journal| author=Hossack KF, Leddy CL, Johnson AM, Schrier RW, Gabow PA| title=Echocardiographic findings in autosomal dominant polycystic kidney disease. | journal=N Engl J Med | year= 1988 | volume= 319 | issue= 14 | pages= 907-12 | pmid=3419455 | doi=10.1056/NEJM198810063191404 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3419455 }} </ref>
 
===Complications===
*Common complications of ADPKD include:<ref name="pmid3565428">{{cite journal| author=Schwab SJ, Bander SJ, Klahr S| title=Renal infection in autosomal dominant polycystic kidney disease. | journal=Am J Med | year= 1987 | volume= 82 | issue= 4 | pages= 714-8 | pmid=3565428 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3565428 }} </ref><ref name="pmid8198379" /><ref name="pmid2365280‎">{{cite journal| author=Gabow PA, Johnson AM, Kaehny WD, Manco-Johnson ML, Duley IT, Everson GT| title=Risk factors for the development of hepatic cysts in autosomal dominant polycystic kidney disease. | journal=Hepatology | year= 1990 | volume= 11 | issue= 6 | pages= 1033-7 | pmid=2365280‎ | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2365280 }} </ref><ref name="pmid17699192‎">{{cite journal| author=Bae KT, Zhu F, Chapman AB, Torres VE, Grantham JJ, Guay-Woodford LM et al.| title=Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort. | journal=Clin J Am Soc Nephrol | year= 2006 | volume= 1 | issue= 1 | pages= 64-9 | pmid=17699192‎ | doi=10.2215/CJN.00080605 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699192 }} </ref><ref name="pmid2365280‎" /><ref name="pmid17434405">{{cite journal| author=Torres VE, Harris PC, Pirson Y| title=Autosomal dominant polycystic kidney disease. | journal=Lancet | year= 2007 | volume= 369 | issue= 9569 | pages= 1287-301 | pmid=17434405 | doi=10.1016/S0140-6736(07)60601-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17434405 }} </ref><ref name="pmid11134244‎">{{cite journal| author=Torres VE, Cai Y, Chen X, Wu GQ, Geng L, Cleghorn KA et al.| title=Vascular expression of polycystin-2. | journal=J Am Soc Nephrol | year= 2001 | volume= 12 | issue= 1 | pages= 1-9 | pmid=11134244‎ | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11134244 }} </ref><ref name="pmid11752048">{{cite journal| author=Pirson Y, Chauveau D, Torres V| title=Management of cerebral aneurysms in autosomal dominant polycystic kidney disease. | journal=J Am Soc Nephrol | year= 2002 | volume= 13 | issue= 1 | pages= 269-76 | pmid=11752048 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11752048 }} </ref><ref name="pmid3419455">{{cite journal| author=Hossack KF, Leddy CL, Johnson AM, Schrier RW, Gabow PA| title=Echocardiographic findings in autosomal dominant polycystic kidney disease. | journal=N Engl J Med | year= 1988 | volume= 319 | issue= 14 | pages= 907-12 | pmid=3419455 | doi=10.1056/NEJM198810063191404 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3419455 }} </ref>
**[[Urinary tract infection|Urinary tract infections]]
**[[Pyelonephritis]]
**[[Cyst]] [[infection]]
**[[Nephrolithiasis]]
**[[Hepatic]] [[cyst]]
**[[Cyst]] [[hemorrhage]]
**[[Cyst]] [[torsion]]
**[[Intracranial aneurysms]]
**[[Thoracic aortic aneurysm|Thoracic aortic aneurysms]]
**[[Coronary artery aneurysm|Coronary artery aneurysms]]
**[[Mitral valve prolapse]]
**[[Diverticulosis]]
**[[End stage renal disease|End stage renal disease (ESRD)]]
 
* Common complications of ARPKD include:<ref name="pmid95870643">{{cite journal| author=Zerres K, Rudnik-Schöneborn S, Steinkamm C, Becker J, Mücher G| title=Autosomal recessive polycystic kidney disease. | journal=J Mol Med (Berl) | year= 1998 | volume= 76 | issue= 5 | pages= 303-9 | pmid=9587064 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9587064  }}</ref><ref name="pmid167674053">{{cite journal| author=Sweeney WE, Avner ED| title=Molecular and cellular pathophysiology of autosomal recessive polycystic kidney disease (ARPKD). | journal=Cell Tissue Res | year= 2006 | volume= 326 | issue= 3 | pages= 671-85 | pmid=16767405 | doi=10.1007/s00441-006-0226-0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16767405  }}</ref><ref name="pmid127280913">{{cite journal| author=Guay-Woodford LM, Desmond RA| title=Autosomal recessive polycystic kidney disease: the clinical experience in North America. | journal=Pediatrics | year= 2003 | volume= 111 | issue= 5 Pt 1 | pages= 1072-80 | pmid=12728091 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12728091  }}</ref>
** [[Congenital hepatic fibrosis]]
** [[Portal hypertension]]
** [[Pulmonary]] [[hypoplasia]]
** [[Chronic]] [[lung]] [[disease]]
** [[Biliary]] [[dysgenesis]]
** Recurrent [[ascending cholangitis]]
 
===Prognosis===
Autosomal dominant polycystic kidney disease (ADPKD):
*Approximately 60% of patients suffer from [[flank pain]] often requiring [[cyst]] [[decompression]] [[surgery]]. Expanding [[cysts]] can often by complicated by [[hemorrhage]] that self-resolves but usually causes significant [[pain]].<ref name="pmid8198379" />
*Generally, [[PKD1]] [[mutants]] have more severe [[renal disease]] with mean age at onset of [[ESRD]] around 50 years compared to 75 years in [[PKD2]] [[mutants]]. But, regardless of the mutation, 50% of ADPKD patients will reach [[ESRD]] by age 60 years.<ref name="pmid10023895">{{cite journal| author=Hateboer N, v Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL et al.| title=Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. | journal=Lancet | year= 1999 | volume= 353 | issue= 9147 | pages= 103-7 | pmid=10023895 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10023895 }} </ref>
*[[Hematuria]] can be seen in ADPKD especially in advanced cases; however, overt [[proteinuria]] is usually uncommon in the context of ADPKD, and [[proteinuria]] > 1 g/day should prompt the consideration of a second disease process.<ref name="pmid1496966">{{cite journal| author=Gabow PA, Duley I, Johnson AM| title=Clinical profiles of gross hematuria in autosomal dominant polycystic kidney disease. | journal=Am J Kidney Dis | year= 1992 | volume= 20 | issue= 2 | pages= 140-3 | pmid=1496966 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1496966 }} </ref><ref name="pmid8198379" />
*Several factors have been linked to a worse renal outcome (renal function for given age) including early age at diagnosis, male gender, uncontrolled [[hypertension]], [[left ventricular hypertrophy]], [[cystic]] [[liver]], gross [[hematuria]], larger [[kidney]] [[volume]], and [[urinary tract infections]].<ref name="pmid1614046">{{cite journal| author=Gabow PA, Johnson AM, Kaehny WD, Kimberling WJ, Lezotte DC, Duley IT et al.| title=Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. | journal=Kidney Int | year= 1992 | volume= 41 | issue= 5 | pages= 1311-9 | pmid=1614046 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1614046 }} </ref>
*The [[aneurysms]] are usually asymptomatic and the mean age at rupture is at 39 years, 12 years younger than in the general population.<ref name="pmid17434405" />
*Significant [[diverticulosis]] can be seen in more than half of ADPKD patients especially those in [[ESRD]] on [[hemodialysis]].<ref name="pmid10695753‎">{{cite journal| author=Lederman ED, McCoy G, Conti DJ, Lee EC| title=Diverticulitis and polycystic kidney disease. | journal=Am Surg | year= 2000 | volume= 66 | issue= 2 | pages= 200-3 | pmid=10695753‎ | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10695753 }} </ref>
Autosomal recessive polycystic kidney disease (ARPKD):
* Half of ARPKD patients usually progress to [[ESRD]] by the age of 10.
* Other morbidities include [[growth retardation]], recurrent [[Urinary tract infection|UTIs]], and [[portal hypertension]] due to [[liver]] involvement.<ref name="pmid12728091">{{cite journal| author=Guay-Woodford LM, Desmond RA| title=Autosomal recessive polycystic kidney disease: the clinical experience in North America. | journal=Pediatrics | year= 2003 | volume= 111 | issue= 5 Pt 1 | pages= 1072-80 | pmid=12728091 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12728091  }}</ref>
* [[Mortality]] is still significantly elevated with around one-fourth of patients dying in the first year of life.
* The first month is usually the most critical period with a [[mortality rate]] of approximately 15%..<ref name="pmid127280912">{{cite journal| author=Guay-Woodford LM, Desmond RA| title=Autosomal recessive polycystic kidney disease: the clinical experience in North America. | journal=Pediatrics | year= 2003 | volume= 111 | issue= 5 Pt 1 | pages= 1072-80 | pmid=12728091 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12728091  }}</ref>
* A significant portion of these patients have varying degrees of [[pulmonary]] [[hypoplasia]] that is incompatible with life related to the massive intra-abdominal size of the [[kidneys]].<ref name="pmid167674052">{{cite journal| author=Sweeney WE, Avner ED| title=Molecular and cellular pathophysiology of autosomal recessive polycystic kidney disease (ARPKD). | journal=Cell Tissue Res | year= 2006 | volume= 326 | issue= 3 | pages= 671-85 | pmid=16767405 | doi=10.1007/s00441-006-0226-0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16767405  }}</ref>
* Patients with mild [[pulmonary]] [[hypoplasia]] might develop [[chronic]] [[lung]] [[disease]] some of which require [[ventilation]] support.
* The prognosis improves in patients that survive the first few months of life.
* [[Portal hypertension]] secondary to [[hepatic fibrosis]] is often the major cause of [[mortality]] in these patients.<ref name="pmid95870642">{{cite journal| author=Zerres K, Rudnik-Schöneborn S, Steinkamm C, Becker J, Mücher G| title=Autosomal recessive polycystic kidney disease. | journal=J Mol Med (Berl) | year= 1998 | volume= 76 | issue= 5 | pages= 303-9 | pmid=9587064 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9587064  }}</ref>
* Survival at 15 years ranges from 50 to 80%. Sixty percent of these patients will not require any [[renal replacement therapy]]. <ref name="pmid11477168">{{cite journal| author=Fonck C, Chauveau D, Gagnadoux MF, Pirson Y, Grünfeld JP| title=Autosomal recessive polycystic kidney disease in adulthood. | journal=Nephrol Dial Transplant | year= 2001 | volume= 16 | issue= 8 | pages= 1648-52 | pmid=11477168 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11477168  }}</ref>


==References==
==References==
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[[Category:Up-To-Date]]
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2], Serge Korjian, Yazan Daaboul

Overview

The earliest clinical signs of disease in patients with ADPKD include impaired renal concentrating capacity and hypertension. Other signs include flank pain, nephrolithiasis and urinary tract infections. In general half of the patients diagnosed with ADPKD will progress to ESRD by age 60. PDK1 mutants usually progress faster than PDK2 mutants. Factors associated with worse renal outcome include early age at diagnosis, male gender, uncontrolled hypertension, left ventricular hypertrophy, and cystic liver. Extra-renal manifestations in ADPKD include hepatic cysts usually more prevalent in women and with advancing age and declining renal function. Cysts can also be seen in the seminal vesicles, pancreas, and arachnoid membrane. Furthermore, the development of intracranial aneurysms can be a lethal complication in ADPKD patients whose risk is closely linked to the family history of aneurysms. Mitral valve prolapse is also a common cardiac manifestation seen in 25% of patients. Most cases of ARPKD present in the neonatal period with some disease findings detected on prenatal ultrasound. Most feared and common complication of ARPKD is pulmonary hypoplasia. Half of ARPKD patients usually progress to ESRD by age of 10. The prognosis of ARPKD improves in patients who survive the first few months of life. Survival at 15 years for patients of ARPKD ranges from 50% - 80%.

Natural History, Complications, and Prognosis

Natural History

Autosomal dominant polycystic kidney disease (ADPKD):

  • The earliest detectable functional aberration seen in patients with ADPKD is impaired concentrating capacity with a suboptimal increase in urinary osmolality following water deprivation.[1]
  • The second early manifestation of disease is hypertension. Up to 75% of patients with ADPKD on imaging without any renal insufficiency are hypertensive.[2]
  • Even in young patients, 50% of those aged 20-34 years are hypertensive despite normal renal function.[3]
  • Overt clinical signs and symptoms of renal disease usually appear during the fourth or fifth decade.[4]

Autosomal recessive polycystic kidney disease (ARPKD):

  • Most affected individuals present in the neonatal period with some disease findings detected in prenatal obstetric ultrasounds.[5]
  • The most common initial findings in ARPKD patients involve abnormal renal structure and function.[6]
  • Approximately 30% of patients have no lab abnormalities at presentation.

Complications

Prognosis

Autosomal dominant polycystic kidney disease (ADPKD):

Autosomal recessive polycystic kidney disease (ARPKD):

References

  1. ↑ Gabow PA, Kaehny WD, Johnson AM, Duley IT, Manco-Johnson M, Lezotte DC; et al. (1989). "The clinical utility of renal concentrating capacity in polycystic kidney disease". Kidney Int. 35 (2): 675–80. PMID 2709672.
  2. ↑ Gabow PA (1990). "Autosomal dominant polycystic kidney disease--more than a renal disease". Am J Kidney Dis. 16 (5): 403–13. PMID 2239929.
  3. ↑ Kelleher CL, McFann KK, Johnson AM, Schrier RW (2004). "Characteristics of hypertension in young adults with autosomal dominant polycystic kidney disease compared with the general U.S. population". Am J Hypertens. 17 (11 Pt 1): 1029–34. doi:10.1016/j.amjhyper.2004.06.020. PMID 15533729.
  4. ↑ 4.0 4.1 4.2 4.3 Fick GM, Gabow PA (1994). "Natural history of autosomal dominant polycystic kidney disease". Annu Rev Med. 45: 23–9. doi:10.1146/annurev.med.45.1.23. PMID 8198379.
  5. ↑ Sweeney WE, Avner ED (2006). "Molecular and cellular pathophysiology of autosomal recessive polycystic kidney disease (ARPKD)". Cell Tissue Res. 326 (3): 671–85. doi:10.1007/s00441-006-0226-0. PMID 16767405.
  6. ↑ Zerres K, Rudnik-Schöneborn S, Steinkamm C, Becker J, Mücher G (1998). "Autosomal recessive polycystic kidney disease". J Mol Med (Berl). 76 (5): 303–9. PMID 9587064.
  7. ↑ Schwab SJ, Bander SJ, Klahr S (1987). "Renal infection in autosomal dominant polycystic kidney disease". Am J Med. 82 (4): 714–8. PMID 3565428.
  8. ↑ 8.0 8.1 Gabow PA, Johnson AM, Kaehny WD, Manco-Johnson ML, Duley IT, Everson GT (1990). "Risk factors for the development of hepatic cysts in autosomal dominant polycystic kidney disease". Hepatology. 11 (6): 1033–7. PMID 2365280‎ Check |pmid= value (help).
  9. ↑ Bae KT, Zhu F, Chapman AB, Torres VE, Grantham JJ, Guay-Woodford LM; et al. (2006). "Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort". Clin J Am Soc Nephrol. 1 (1): 64–9. doi:10.2215/CJN.00080605. PMID 17699192‎ Check |pmid= value (help).
  10. ↑ 10.0 10.1 Torres VE, Harris PC, Pirson Y (2007). "Autosomal dominant polycystic kidney disease". Lancet. 369 (9569): 1287–301. doi:10.1016/S0140-6736(07)60601-1. PMID 17434405.
  11. ↑ Torres VE, Cai Y, Chen X, Wu GQ, Geng L, Cleghorn KA; et al. (2001). "Vascular expression of polycystin-2". J Am Soc Nephrol. 12 (1): 1–9. PMID 11134244‎ Check |pmid= value (help).
  12. ↑ Pirson Y, Chauveau D, Torres V (2002). "Management of cerebral aneurysms in autosomal dominant polycystic kidney disease". J Am Soc Nephrol. 13 (1): 269–76. PMID 11752048.
  13. ↑ Hossack KF, Leddy CL, Johnson AM, Schrier RW, Gabow PA (1988). "Echocardiographic findings in autosomal dominant polycystic kidney disease". N Engl J Med. 319 (14): 907–12. doi:10.1056/NEJM198810063191404. PMID 3419455.
  14. ↑ Zerres K, Rudnik-Schöneborn S, Steinkamm C, Becker J, Mücher G (1998). "Autosomal recessive polycystic kidney disease". J Mol Med (Berl). 76 (5): 303–9. PMID 9587064.
  15. ↑ Sweeney WE, Avner ED (2006). "Molecular and cellular pathophysiology of autosomal recessive polycystic kidney disease (ARPKD)". Cell Tissue Res. 326 (3): 671–85. doi:10.1007/s00441-006-0226-0. PMID 16767405.
  16. ↑ Guay-Woodford LM, Desmond RA (2003). "Autosomal recessive polycystic kidney disease: the clinical experience in North America". Pediatrics. 111 (5 Pt 1): 1072–80. PMID 12728091.
  17. ↑ Hateboer N, v Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL; et al. (1999). "Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group". Lancet. 353 (9147): 103–7. PMID 10023895.
  18. ↑ Gabow PA, Duley I, Johnson AM (1992). "Clinical profiles of gross hematuria in autosomal dominant polycystic kidney disease". Am J Kidney Dis. 20 (2): 140–3. PMID 1496966.
  19. ↑ Gabow PA, Johnson AM, Kaehny WD, Kimberling WJ, Lezotte DC, Duley IT; et al. (1992). "Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease". Kidney Int. 41 (5): 1311–9. PMID 1614046.
  20. ↑ Lederman ED, McCoy G, Conti DJ, Lee EC (2000). "Diverticulitis and polycystic kidney disease". Am Surg. 66 (2): 200–3. PMID 10695753‎ Check |pmid= value (help).
  21. ↑ Guay-Woodford LM, Desmond RA (2003). "Autosomal recessive polycystic kidney disease: the clinical experience in North America". Pediatrics. 111 (5 Pt 1): 1072–80. PMID 12728091.
  22. ↑ Guay-Woodford LM, Desmond RA (2003). "Autosomal recessive polycystic kidney disease: the clinical experience in North America". Pediatrics. 111 (5 Pt 1): 1072–80. PMID 12728091.
  23. ↑ Sweeney WE, Avner ED (2006). "Molecular and cellular pathophysiology of autosomal recessive polycystic kidney disease (ARPKD)". Cell Tissue Res. 326 (3): 671–85. doi:10.1007/s00441-006-0226-0. PMID 16767405.
  24. ↑ Zerres K, Rudnik-Schöneborn S, Steinkamm C, Becker J, Mücher G (1998). "Autosomal recessive polycystic kidney disease". J Mol Med (Berl). 76 (5): 303–9. PMID 9587064.
  25. ↑ Fonck C, Chauveau D, Gagnadoux MF, Pirson Y, Grünfeld JP (2001). "Autosomal recessive polycystic kidney disease in adulthood". Nephrol Dial Transplant. 16 (8): 1648–52. PMID 11477168.

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