Assounga, A G H

Gombet, T

Ibara, J R

Makosso, E

Yacoubou, Y

South African Medical Journal (SAMJ)

Autosomal dominant polycystic kidney disease (ADPKD), acommon  hereditary disease worldwide, is not welldocumented in Africa, with only a few reports available.1-3ADPKD is one of the most frequently inherited disorders, witha prevalence ranging from 1/400 to 1/1 000 in Europe andAmerica.4 Much progress has been made in characterising thegenes involved and their products. ADPKD is characterised byan adult clinical onset, the presence of at least three kidneycysts bilaterally, and an autosomal dominant transmission.4ADPKD is reported to be associated with at least two genes.The PKD1 gene is located on chromosome 16p3.3, and thePKD2 gene on chromosome 4q21-23. 5-7 Their products aremembrane-bound proteins that are expressed in most epithelialtissue and the brain. 7 They interact and function as hetero-dimers. Patients with ADPKD have higher expression of bothalleles, raising the question whether PKD1 is the triggeringfactor for cyst formation or whether it is a secondary factor. Ithas been associated with the maturation and repair of the renaltubule. The PKD1 gene is associated with early and severesymptoms, while PKD2 and other genes are associated withlate and less severe symptoms.8 In light of the diversity ofgenes involved we examined the expression of ADPKD inCongolese patients. The objective of this study was to analysethe clinical features of ADPKD in patients admitted to theDepartment of Nephrology and Haemodialysis at BrazzavilleUniversity Hospital from December 1989 to February 1995, aswell as the clinical features of their respective family members.Materials and methodsAll patients admitted to the Department of Nephrology andHaemodialysis from December 1989 to March 1994 who had atleast three cysts in each kidney on abdominal ultrasonography,were at least 20 years old, and had a family history suggestiveof hereditary disease were included. Patients were excluded ifthere was no family history of polycystic kidney disease or ifrenal cysts were absent in relatives. Patients who developedrenal cysts after a long period of dialysis were also excluded.Seven patients were identified.After giving informed consent, relatives of patientsunderwent a clinical examination, a serum creatinine test,urinalysis, an abdominal ultrasound scan, and monthly follow-up for 6 months if found to have polycystic kidney disease.542July 2003, Vol. 93, No. 7  SAMJORIGINAL ARTICLESLiver cysts in Congolese patients with autosomal dominantpolycystic kidney disease follow a family patternA G H Assounga, Y Yacoubou, E Makosso, J R Ibara, T GombetBackground. It is now well established that at least two genesare associated with autosomal dominant polycystic kidneydisease (ADPKD).Objective. To analyse the clinical expression of ADPKD inCongolese patients and to compare ADPKD expressionbetween families.Methods. Following informed consent, ADPKD patientsadmitted to Brazzaville University Hospital (Congo) werereviewed and their relatives aged 20 years and older werescreened by means of a clinical examination, abdominalultrasound, urinalysis and determination of serum creatinine.Results. We found 7 patients with ADPKD, belonging to 7distinct families, and identified 100 relatives of whom 50,aged from 20 to 68 years, were diagnosed as having ADPKD.Polycystic kidney disease was associated with polycystic liverin 4 families. In the remaining 3 families no liver cysts werefound. No family had a mixture of members with kidneycysts only and members with kidney and liver cysts. Thisfinding was age-independent.Conclusion. Liver cysts follow a family pattern in our ADPKDpatients. We suggest that our patients may carry at least twodifferent genes for ADPKD, one of which may be associatedwith renal cysts alone and other with both renal and liver cysts.S Afr Med J 2003; 93: 542-544.Department of Nephrology and Haemodialysis, Centre Hospitalier Universitair eand Marien Ngouabi University, Brazzaville, Congo A G H Assounga, MD, MSc, CES, PhDY Yacoubou,MDDepartment of Radiology, Centre Hospitalier Universitaire and Manen NgouabiUniversity, Brazzaville, CongoE Makosso, MD, DISDepartment of Gastroenterology, Centre Hospitalier Universitaire and MarienNgouabi University, Brazzaville, Congo J R Ibara, MD, DISDepartment of Cardiology, Centre Hospitalier Universitaire and Marien Ngouabi University, Brazzaville, CongoT Gombet, MD, CESORIGINAL ARTICLES543July 2003, Vol. 93, No. 7  SAMJThe chi-square test or Fisher’s exact test was used tocompare different groups, using the Instat 2 software program(GraphPad Instat, San Diego, Calif., USA).ResultsWe found that the patients who fulfilled the criteria forADPKD belonged to 7 distinct families. Of 100 relatives ofpatients screened, 50 were found to have ADPKD. The totalnumber of patients with ADPKD was therefore 57 (7symptomatic and 50 asymptomatic). Ages ranged from 25 to 68years. There were 34 men and 23 women.Clinical features are summarised in Table I (Figs 1 and 2).Clinical symptoms and signs seemed more severe in the 4families with associated liver cysts, but the difference was notstatistically significant (p > 0.05), except for the presence of analfistula (p = 0.0012). A high prevalence of anal fistula was foundin one of the families with polycystic liver and kidney disease;no colonoscopy was done to search for diverticulitis. Nopancreatic cysts or other organ cysts were found. No search forcerebral aneurysm was carried out. The pattern of organinvolvement was similar in patients within the same family.Polycystic kidney disease was associated with polycystic liverin 4 families. In the remaining 3 families, no liver cysts werefound. No family included a mixture of patients with kidneycysts only and patients with kidney and liver cysts. Thisfinding was age-independent. In families with ADPKD where 1member had hepatic cysts all the relatives with kidney cystsalso had hepatic cysts (Fig. 3). The presence or absence ofhepatic cyst follows a family pattern (Figs 3 and 4). All familiesran true to form, showing either renal cysts alone or both renaland liver cysts, but never a combination of both patternswithin a single family.DiscussionADPKD is prevalent in the Congo and its clinical expressionmirrors that described elsewhere. The pattern of clinicalmanifestation suggests that more than one gene is involved. In4 of 7 families, kidney cysts were associated with liver cysts.The association of liver cysts with kidney cysts is thought to bea poor prognostic factor.9 In our study, patients with onlykidney cysts seemed to have less severe manifestations thanthose with both kidney and liver cysts; however the differencewas not statistically significant. Clinical manifestations in ourADPKD patients were similar to those described elsewhere. 1-4However, the incidence of ADPKD is lower than in Europe orthe USA. A lower incidence of ADPKD has been reported inblack Americans compared with whites.4 Clinical expression ischaracterised by low back pain, abdominal mass andhaematuria as main complaints leading to the diagnosis ofADPKD. Hypertension was found in 7% of our patients.Table I. Clinical manifestations of ADPKD according topresence or absence of liver cystsADPKD ADPKD patients patientswith liver withoutClinical cysts liver cysts Totalmanifestations N % N % N %Number of families 4 57 3 43 7 100Number of patients 37 65 20 35 57 100Hypertension 5 13.5 2 10 7 12.3 (p > 0.05)Renal failure 6 16.2 2 10 8 14    ( p > 0.05)Abdominal pain 4 11 3 15 7 12M a c roscopic haematuria 7 19 4 19 11 19.3Urinary tract infection 4 10.8 3 15 7 12.3Stroke 1 2.7 0 0 1 1.8Anal fistula 2 0 2 5 0 0 2 0 35  (p = 0.0012)Fig. 1.  Ultrasound scan of a kidney showing multiple cysts.Fig. 2.  Ultrasound scan of a liver showing multiple cysts.544July 2003, Vol. 93, No. 7  SAMJORIGINAL ARTICLESDuring the same period the prevalence of hypertension amonginpatients was 9.46%. Chronic renal failure (CRF) was presentin 7% of our patients. ADPKD represents 2% of patients withCRF. Development of liver cysts in ADPKD has been associatedwith female gender, pregnancy, age, and severity of renaldisease.9ADPKD genes are widely expressed. Polycystin 1 andpolycystin 2 have been found in all major organs, including theliver and kidney. The highest expression of polycystin has beenfound in the brain. The kidney has an intermediate levelexpression of polycystin. In normal individuals, polycystin isfound in the cytoplasm and is markedly present in the lateraljunction of epithelial cells of the distal tubule in the normalkidney, and of the proximal tubule in the injured kidney. Inpatients with ADPKD there is an over-expression of polycystin1 and polycystin 2 compared with normal controls. Polycystinis expressed with variable intensity in the epithelial lining ofboth renal and liver cysts and is more intense in the cytoplasmthan in the lateral membrane.5,7The progression of ADPKD is dependent of four groups offactors: the germline mutation (PKD1 or PKD2 gene), themodifying genes, the somatic mutations, and environmentfactors.10 Several mutations of the PKD1 and PKD2 genes havebeen reported in patients with ADPKD. A mutation in eitherthe PKD1 and PKD2 gene that affects the interaction ofpolycystin 1 and polycystin 2 is believed to be responsible forthe cyst formation.10 A defect in both copies of PKD1 genes isrequired for a defunct polycystin. The resulting defect in fluidmovement and epithelial distribution will alter the normalarchitecture leading to cyst formation. Environmental factorsthe progression of cysts include endotoxins and acidifyingagents, which accelerate cyst progression in mice, whereasalkalising agents and a low-protein diet slow progression. 10To our knowledge, although the association of liver cystswith ADPKD is well established in individual patients, this isthe first report indicating that the presence of liver cysts inADPKD follows a family pattern. We suggest that our patientsmay carry at least two different genes for ADPKD, one ofwhich may be associated with renal cysts alone, and the otherwith both renal and liver cysts. A genetic analysis is warrantedin order to determine whether PKD1, PKD2 or other genes areinvolved in our patients.1. Kheder A, Ben Hamida F, el Younsi F, et al. Dominant polycystic renal disease. Study of 105cases. Rev Med Interne 1992; 28: 241-242.2. Diouf B, Dia D, Ka MM, Ka EF, Diop TM. Autosomal dominant polycystosis in the hospitalmilieu in Dakar (Senegal). Dakar Med 1998; 43: 205-208.3. Sulieman SM, Elsadig M, Fesseha S, et al. Autosomal dominant polycystic kidney disease inSudan. Saudi J Kidney Dis Transplant 1996; 7: S12-S14.4. Gabouw PA. Autosomal dominant polycystic kidney disease. N Engl J Med 1993; 329: 333-342.5. Ward CJ, Turley H, Ong ACM, et al. Polycystin, the polycystic kidney disease 1 protein, isexpressed by ephithelial cells in fetal, adult, and polycystic kidney. Proc Natl Acad Sci USA1996; 93: 1524-1528.6. Mochizuki T, Wu G, Hayashi T, et al. PKD2, a gene for polycystic kidney disease that encodesan integral membrane protein. Science 1996; 272: 1339-1342.7. Ibraghimov-Beskrovnaya O, Dackowski WR, Foggensteiner L, et al. Polycystin: in vitrosynthesis, in vivo tissue expression, and subcellular localization identify a large membrane-associated protein. Proc Natl Acad Sci USA 1997; 94: 6397-6402.8. Hateboer N, van Dijk MA, Bogdanova N, et al. Comparison of phenotypes of polycystickidney disease types 1 and 2. European PKD1-PKD2 study group. Lancet 1999; 353: 103-107.9. Gabow PA, Johnson AM, Keahny WD, Manco-Johnson ML, Duley IT, Everson GT. Riskfactors for the development of hepatic cysts in autosomal dominant polycystic kidneydisease. Hepatology 1990; 11: 1033-1037.10. Peters DJM, Breuning MH. Autosomal dominant kidney disease: modification of diseaseprogression. Lancet 2001; 358: 1439-1444.Fig. 3.  Pedigree of a family with patients with both multiple renaland liver cysts.Fig. 4.  Pedigree of a family with patients with multiple cysts only inthe kidney.

Liver cysts in Congolese patients with autosomal dominant polycystic kidney disease follow a family pattern

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Liver cysts in Congolese patients with autosomal dominant polycystic kidney disease follow a family pattern

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South African Medical Journal (SAMJ)