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Year : 2001  |  Volume : 17  |  Issue : 2  |  Page : 81-83

Progression of renal failure in adult polycystic kidney disease

Department of Nephrology, Sri Sathya Sai Institute of Higher Medical Sciences, Prashantigram, Anantapur District, Andhra Pradesh, India

Correspondence Address:
V Sivakumar
Head of Nephrology, Sri Sathya Sai Institute of Higher Medical Sciences, Prashantigram - 515134, Anantapur District, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

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Keywords: Progression; Renal Failure; Adult; Polycystic Kidney Disease

How to cite this article:
Sivakumar V. Progression of renal failure in adult polycystic kidney disease. Indian J Urol 2001;17:81-3

How to cite this URL:
Sivakumar V. Progression of renal failure in adult polycystic kidney disease. Indian J Urol [serial online] 2001 [cited 2023 Jan 28];17:81-3. Available from:

Adult Polycystic Kidney Disease (ADPKD) is a com­mon hereditary disorder resulting in progressive renal failure accounting for about 10% of the cases of End Stage Renal Disease (ESRD). Though renal cysts look innocent when they occur alone, but in large numbers as in patients of ADPKD they can lead to progressive renal parenchymal destruction and chronic renal fail­ure. Each human kidney has about one million nephrons and in ADPKD, about 1% to 2% of nephrons only show cyst formation. It is intriguing that how such a small percentage of nephron involvement by cystic formation can lead to loss of renal function. This gives an insight that something else also must be responsible in addition to cyst formation to cause renal failure. This view is also supported by the observation that even though there are multiple cysts in all the patients of ADPKD, about 50% only go into renal failure suggesting again that apart from cysts some other factors must be responsible for progression to renal failure. [1],[2],[3],[4],[5],[6]

The literature review suggest that in addition to the mechanical compression and destruction of surround­ing parenchyma by the expanding cysts, there are sev­eral other factors like the genotype, gender, hypertension, apoptosis, abnormal renal ammonia handling, hypoka­laemia, hyperfiltration, interstitial fibrosis, repeated uri­nary tract infections, gross haematuria are cited as factors resulting in progression of renal failure. [3],[7]

In general, Type I ADPKD genotype develop renal fail­ure earlier than Type II PKD. About 80% of ADPKD patients show Type I PKD genotype and about 10% show Type II genotype and the remaining are due to putative Type III genetic mutation. The tendency for ESRD to develop within families more homogeneously than be­tween the families suggests that genetic background plays a role. In general males develop renal failure earlier to women. Similar phenomenon was observed in experimental rats also. However, in women with four or more children, the decline in renal function appear to be accelerated. [7],[8],[9],[10]

The incidence of hypertension is about 50 to 70% in ADPKD. Activation of renin angiotensin system due to stretch and com­pression of renal vasculature by the enlarging cysts, sodium retention with plasma volume expansion, endothelin liberation from cyst fluid, epidermal growth factor mediated renal vascu­lar constriction are considered in the pathogenesis of hyperten­sion and progression of renal failure in ADPKD. Marked renal arteriolar sclerosis is a prominent finding reflecting particular susceptibility of renal vessels to hypertension in ADKPD pa­tients. Immuno-histochemical studies of kidneys in patients of ADPKD revealing hyperplasia of juxta-glomerular apparatus. Increase in renin containing cells, extensive distribution of renin containing cells in arteriolar wall, away from vascular pole, areas of mesangial metaplasia into myoepitheliod renin-secret­ing cells, confirm the role of renin in mediation of hyperten­sion which in turn leads to progressive arteriolar constriction, sclerosis, renal ischaemia and failure. In addition to arteriolar constriction and ischaemia, Angiotensin II also contributes to renal fibrosis by way of stimulating mesangial cell growth and matrix formation. Hypertension is observed more in its inci­dence and severity with increasing renal volume and number of cysts in ADPKD patients. [6],[7],[9],[10],[11],[12],[13],[14]

Apoptosis is a programmed cell death in which each cell actively synthesizes new RNA and proteins to mediate its own demise. Normally large scale apoptosis occurs during metanephric development to serve to match the number of collecting ducts developed from the ureteric bud to number of tubules developing from the metanephric mesenchyme and after all the differentiated nephrons are formed the ma­ture kidney no longer generates new nephrons. In cell cul­ture experiments of primary cultures and serially passaged polycystic kidney cells in vitro, the polycystic kidney cells show molecular features of apoptosis even when the factors like uraemia, ischaemia, compression and obstruction are absent. This suggests that apoptotic cell death may be an innate abnormality of the cells of polycystic kidneys. In addition to the apoptotic activity in polycystic kidneys, ves­sel walls also show apoptosis resulting in aneurismal for­mation in experimental mice. This suggests the possibility that apoptosis is a generalized process and not confined only to polycystic kidney cells. Probably the apoptotic ac­tivity initiated by cysts may elaborate paracrine factors ca­pable of initiating apoptosis in surrounding normal cells or by acting on modifier genes protecting from apoptotic stimuli. Thus the apoptosis allegedly initiated by cysts ap­pear to cause disappearance of neighbouring glomeruli and tubular cells and thus reduce the number of functioning nephrons out of proportion to the number of existing cysts in polycystic kidneys. [1],[2],[7],[15]

Patients of ADPKD develop renal concentration defect prior to any reduction in glomerular filtration. Ammonia is produced in renal cortical region and is excreted into renal medullary tubule with the help of cortico-medullary concentration gradient. Ammonia accumulates in renal me­dulla when the concentration gradient is disrupted. Am­monia can activate complement and result in interstitial inflammation, mononuclear-mediated cytokine release, cyst formation, growth and interstitial fibrosis and ulti­mately progression of renal failure. Potassium, the most prevalent intracellular cation, when deficient can result in marked alterations in cell structure and function. Potas­sium deficiency in the proximal tubular cells in ADPKD patients leads to decreased intracellular pH, increased am­monia production, increased citrate absorption, intersti­tial inflammatory infiltration with mononuclear cells, activation of complement system by increased ammonia production and ultimately leads to interstitial fibrosis and progression of renal failure. [3],[7],[16],[17],[18],[19],[20]

Cysts are the hallmarks of ADPKD, contributing to kid­ney size. The relation between kidney size, volume and progression to renal failure is debatable in the light of ex­isting findings in the literature. The aberrant epithelia that comprise cysts may be interacting adversely with extra­cystic elements in the kidneys. Cyst epithelia found to ex­press monocystic chemotactic protein, osteopontin and cyst-activating factor. These factors not only result in cyst growth but also the interstitial inflammatory process and fibrosis in the surrounding parenchyma. Cysts adversely affect the adjacent parenchyma by causing deposition of interstitial collagen and increasing extracellular matrix, interstitial infiltration with macrophages, lymphocytes and fibroblasts, vascular sclerosis and ultimately interstitial fibrosis and tubular atrophy. The vascular sclerosis ob­served in ADPKD patients appear to be more than in pa­tients with comparable renal dysfunction secondary to glomerular disease. There was no evidence of extravasa­tion of tubular fluid into interstitial tissue as evidenced by absence of Tamm-Horsfall protein deposits in the intersti­tium, to cause interstitial inflammation. Surgical decom­pression of the cysts though relieved pressure could not prevent the decline of glomerular filtration rate. This sug­gests that cyst size and number alone is not totally responsible for progression to renal failure. [3],[4],[6],[7],[15],[21],[22],[23],[24],[25],[26],[27]

Though the noncystic nephrons adoptively increase their function initially, by increasing their glomerular filtration to compensate the existing nephron loss, the compensa­tory mechanisms eventually fail and renal function dete­riorates. [6] Thus there are alterable and unalterable factors playing a role in progression to renal failure in ADPKD. However the knowledge of the preventable or alterable factors like control of hypertension, timely detection and management of urinary tract infection, haematuria, dietary modifications to reduce hyperfiltration, correction of hypokalemia and acidosis, etc., help the clinician in pre­venting or retarding the progression of renal failure to a great extent.

   References Top

1.Grantham JJ. Polycystic kidney disease - There goes the neigh­bourhood. N Engl J Med 1995; 333: 56-57.  Back to cited text no. 1    
2.David Woo. Apoptosis and loss of renal tissue in polycystic kidney disease. N En-1 J Med 1995; 333: 18-25.  Back to cited text no. 2    
3.Gabow PA, Johnson AM, Kaehny WD et al. Factors affecting the progression of renal disease in autosomal dominant polycystic kid­ney disease. Kid Int 1992; 41: 1311-1319.  Back to cited text no. 3    
4.Franz KA, Reubi FC. Rate of functional deterioration in polycystic kidney disease. Kid Int 1983; 23: 526-529.  Back to cited text no. 4    
5.Churchill DN, Bear JC, Morgan J et al. Prognosis of adult onset polycystic kidney disease re-evaluated. Kid Int 1984; 26: 190-193.  Back to cited text no. 5    
6.Ritz E, Zeier M, Waldherr R. Progression to renal insufficiency. In: Watson ML, Torres VE (eds) Oxford Press, Oxford 1996; 430-449.  Back to cited text no. 6    
7.Grantham JJ. Mechanisms of progression in autosomal dominant polycystic kidney disease. Kid Int 1997; 52 (Suppl 63): 93-97.  Back to cited text no. 7    
8.Dalgaard OZ. Bilateral polycystic disease of kidneys: A follow-up of two hundred and eighty-four patients and their families. Acta Med Scand 1957; 328: 1-255.  Back to cited text no. 8    
9.Gretz N, Kranzlin B, Pey R, et al. Rat models of autosomal domi­nant polycystic kidney disease. Nephrol Dial Transplant 1996; 11 (Suppl 6): 46-51.  Back to cited text no. 9    
10.Wilson PD, Woodford LG. Pathophysiology and clinical manage­ment of polycystic kidney disease in women. Semin Nephrol 1999; 19: 123-132.  Back to cited text no. 10    
11.Watson ML. Clinical developments in polycystic kidney disease. Nephrol Dial Transplant 1996; 11: 764-766.  Back to cited text no. 11    
12.Chapman AB, Johnson A, Gabow PA, Shrier RW. The renin angi­otensin-aldosterone system and autosomal dominant polycystic kid­ney disease. N En-1 J Med 1990; 323: 1091-1096.  Back to cited text no. 12    
13.Graham PC, Lindop GBM. The anatomy of renin-secreting cell in adult polycystic kidney disease. Kid Int 1988; 33: 1084-1090.  Back to cited text no. 13    
14.Kennefick TM, AL-Nimri MA, Oyama TT et al. Hypertension and renal injury in experimental PKD. Kid Int 1999; 56: 2181-2190.  Back to cited text no. 14    
15.Parfrey PS, Barret BJ. Hypertension in autosomal dominant poly­cystic kidney disease. Curr Opin Nephrol Hypertens 1995; 4; 5: 460-464.  Back to cited text no. 15    
16.Torres VE. New insights into polycystic kidney disease and its treat­ment. Curr Opin Nephrol Hypertens 1998; 7: 159-169.  Back to cited text no. 16    
17.Tones VE, Keith DS, Offord KP, Kon SP, Wilson DM. Renal am­monia in autosomal dominant polycystic kidney disease. Nephron 1979; 24: 198-204.  Back to cited text no. 17    
18.Gabow PA, Kaehny WD. Johnson AM et al. The clinical utility of renal concentrating capacity in polycystic kidney disease. Kid Int 1989; 35: 675-680.  Back to cited text no. 18    
19.Torres VE, Mujwid DK, Wilson DM, Holley KH. Renal cystic dis­ease and ammoniagenesis in Han: SPRD rats. J Am Soc Nephrol 1994; 5: 1193-1200.  Back to cited text no. 19    
20.Alpern RJ, Toto RD. Hypokalemic Nephropathy - A clue to cystogenesis? N Engl J Med 1990; 322: 398-399.  Back to cited text no. 20    
21.Murcia NS, Sweeny WE, Avner ED. New insights into the molecular pathophysiology of polycystic kidney disease. Kid Int 1999; 55: 1187-1197.  Back to cited text no. 21    
22.Gabow PA, Ikle DW, Holmes JH. Polycystic kidney disease: Prospective analysis of non-azotemic patients and family members. Ann Intern Med 1984; 101: 238-247.  Back to cited text no. 22    
23.Gardner Jr KD, Burnside JS, Elzinga WW, Locksley RM. Cytokines in fluids from polycystic kidneys. Kid Int 1991: 39: 718-724.  Back to cited text no. 23    
24.Elzinga LW, Barry JM. Torres VE et al. Cyst decompression sur­gery for autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1992; 2: 1219-1226.  Back to cited text no. 24    
25.LambertPP. Polycystic disease of the kidney. Arch Pathol Lab Med 1947; 44: 34-58.  Back to cited text no. 25    
26.Zeier M, Fehrenbach P. Geberth S et al. Renal histology in poly­cystic kidney disease with incipient and advanced renal failure. Kid Int 1992; 42: 1259-1265.  Back to cited text no. 26    
27.Galtonell VH, Cowley BD, Barash BD et al. Methyl prednisolone retards the progression of inherited polycystic kidney disease in rodents. Am J Kidney Dis 1995; 25: 302-313.  Back to cited text no. 27    


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