Renal artery occlusion in autosomal dominant polycystic kidney disease

Several vascular abnormalities have been reported in autosomal dominant polycystic kidney disease (ADPKD). Occlusion of the renal artery is uncommon in ADPKD and can be associated with hypertension. We report a 38-year-old woman with ADPKD and severe hypertension, abdominal magnetic resonance angiogram and arteriography revealed left renal artery total occlusion. A revascularization approach was not considered feasible and she was given conservative treatment. We review the literature and make some comments about renal artery occlusion in ADPKD. This association should be kept in mind in cases of ADPKD with severe or resistant hypertension.     

Renal and cardiac effects of antihypertensive treatment with ramipril vs metoprolol in autosomal dominant polycystic kidney disease.

BACKGROUND: Hypertension is a common complication in autosomal dominant polycystic kidney disease (ADPKD). This prospective randomized double-blind study was performed to compare the renal and cardiac effects of the ACE inhibitor ramipril and the beta-blocker metoprolol as first line therapy in ADPKD patients with hypertension. METHODS: Forty-six hypertensive ADPKD patients were randomized to either ramipril (n = 23) or metoprolol (n = 23). Twenty-four hour (24-h) ambulatory blood pressure (BP), glomerular filtration rate (GFR) as calculated by the Cockcroft and Gault formula, urinary albumin excretion (albumin/creatinine ratio), and left ventricular mass index (LVMI) were established at baseline and at yearly intervals. The total follow-up was 3 years. Baseline characteristics were similar in both groups. RESULTS: Mean arterial pressure (MAP) decreased significantly in both the ramipril and the metoprolol group (-8 +/- 2 and -6 +/- 2 mmHg; both P < 0.01). There was a significant decline in renal function during follow-up which was similar in patients treated with ramipril or metoprolol (-2.5 +/- 0.7 vs -2.9 +/- 0.8 ml/min/year; P = NS). After the 3 years follow-up, no differences in GFR, LVMI and urinary albumin excretion were observed between the ramipril and the metoprolol group (80.7 +/- 10.7 vs 78.0 +/- 7.6 ml/min, 102.6 +/- 6.8 vs 100.3 +/- 5.4 g/m(2); and 42.6 +/- 12.3 vs 70.3 +/- 32.5 mg/g, respectively; all P = NS). A post-hoc analysis evaluating the effects of BP control, revealed that LVMI increased in patients with standard BP control while it remained stable in patients with rigorous BP control with a significant difference in LVMI between the groups after 3 years of follow-up (110.5 +/- 6.3 vs 90.9 +/- 4.7 g/m(2); P = 0.017). Also, by the end of the study albuminuria was lower in patients with rigorous vs standard BP control (23.5 +/- 6.7 vs 94.8 +/- 35.4 mg/g; P = 0.05). CONCLUSIONS: In our study population of hypertensive ADPKD patients, no differences in renal function, urinary albumin excretion and LVMI were detected between those treated with ramipril or metoprolol, respectively, during a 3 years follow-up. Rigorous BP control prevented an increase in LVMI and reduced urinary albumin excretion, suggesting a crucial role of BP control for slowing progression of cardiac and renal organ damage in ADPKD.     

Pathways of apoptosis in human autosomal recessive and autosomal dominant polycystic kidney diseases

Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of end-stage renal disease in adults. Autosomal recessive (AR) PKD affects approximately 1:20,000 live-born children with high perinatal mortality. Both diseases have abnormalities in epithelial proliferation, secretion, and cell-matrix interactions, leading to progressive cystic expansion and associated interstitial fibrosis. Cell number in a kidney reflects the balance between proliferation and apoptosis. Apoptosis results from extrinsic (ligand-induced, expression of caspase-8) and intrinsic (mitochondrial damage, expression of caspase-9) triggers. Previous studies have suggested a role for apoptosis in PKD cyst formation and parenchymal destruction. Mechanisms underlying apoptosis in human ADPKD and ARPKD were examined by quantitative immunohistochemistry and Western immunoblot analyses of age-matched normal and PKD tissues. Caspase-8 expression was significantly greater in small cysts and normal-appearing tubules than in larger cysts in ADPKD kidneys. Caspase-8 also appeared early in the disease process of ADPKD. In ARPKD, expression of caspase-8 was most pronounced in later stages of the disease and was not confined to a specific cyst size. In conclusion, apoptosis in human ADPKD is an early event, occurring predominantly in normal-appearing tubules and small cysts, and is triggered by an extrinsic factor, but it occurs later in ARPKD.     

Autosomal recessive polycystic kidney disease: long-term outcome of neonatal survivors

 Autosomal recessive polycystic kidney disease causes renal and hepatic dysfunction in childhood. We describe the clinical outcome of 52 children with this diagnosis born between 1950 and 1993. Currently 23 are alive, 24 dead and 5 have been lost to follow-up; 1 has been dialysed and 7 transplanted. Life-table analysis of the patients surviving the 1st month of life revealed an actuarial renal survival of 86% at 1 year and 67% at 15 years. The probability of requiring anti-hypertensive treatment was 39% at 1 year and 60% at 15 years of age. Bleeding from gastro-oesophageal varices occurred in 8 patients at a mean age of 12.5 years, and was preceded by haematological evidence of hypersplenism in 6 of them. The study indicates a relatively good prognosis for patients with this condition who survive the neonatal period and emphasises the importance of early detection and appropriate management of systemic and portal hypertension. Received May 17, 1996; received in revised form and accepted October 29, 1996     

Complications of autosomal dominant polycystic kidney disease in 50 haemodialysed patients. A case-control study

BACKGROUND: The impact of renal and extrarenal manifestations of autosomaldominant polycystic kidney disease (ADPKD) during chronic haemodialysis(HD) has never been assessed in a paired case-control study. METHODS: Comparison of the course of 50 ADPKD patients with 50 matchedcontrol (C) patients who started chronic HD at the same time. RESULTS: Follow-up averaged 48 and 39 months in the ADPKD and C groupsrespectively. Actuarial survival was similar in both groups.Prevalence of renal pain (36 vs 2%, P=0.0001), haematuria (36vs 16%, P<0.03) and renal infection (16 vs 2%, P<0.04)was higher in the ADPKD than in the C group. Nephrectomy duringHD was performed in six ADPKD (in 4 cases in preparation fortransplantation) and in one control patient. Number of patientswith coronary and heart valve complications was similar in bothgroups. Stroke occurred in three patients from both groups.Only two ADPKD patients experienced a single episode of painrelated to liver cyst. Prevalence of severe infection was similarin the ADPKD group (36%) and the C group (28%). Number and durationof hospitalizations were similar in both groups. CONCLUSIONS: The overall outcome of ADPKD patients on maintenance HD is similarto that of HD patients with other primary renal diseases. Complicationsrelated to cystic kidneys are frequent but rarely severe. Extrarenalmanifestations of ADPKD have a limited clinical impact in thisshort-term study.     

Autosomal recessive polycystic kidney disease in 15 Arab children

The study includes 15 children (8 males, 7 females) with autosomal recessive polycystic kidney disease (APRKD) whose ages at diagnosis ranged from 2 days to 7 years (median 10 months). Eleven (73.3%) patients were hypertensive on admission and 1 developed hypertension 4 months later; 5 patients became normotensive after receiving treatment for 18–36 months (mean 23.2 months). Patients were followed for a period of 1–48 months (mean 20.9 months). Glomerular filtration rate remained normal in 7 patients, improved in 4 and deteriorated in 1. Two patients died soon after diagnosis and 1 was lost to follow-up and is assumed dead. Of the 4 patients less than 6 months old at the time of diagnosis, only 1 is alive compared with 10 of 11 presenting after 6 months of age. The cumulative chance of survival from the time of diagnosis was 85% at 3 months and 77% at 6 months. The study highlights the reversible nature of hypertension in ARPKD. Survival is better in patients older than 6 months at the time of diagnosis and those surviving 6 months follow-up.     

Assessment of renal function with color Doppler ultrasound in autosomal dominant polycystic kidney disease

BACKGROUND: Measurement of renal blood flow by color Doppler ultrasound is useful for assessment of renal function in a variety of renal disorders. In autosomal dominant polycystic kidney disease (ADPKD), however, it might be difficult to visualize interlobar arteries because of deformity of renal structure. To evaluate the usefulness of color Doppler in ADPKD, parameters determined by blood flow examination were compared with the results of ordinal renal function tests. METHODS: Twenty-one patients with ADPKD were examined by color Doppler ultrasound measurement. In each patient, 10 interlobar arteries in both kidneys were investigated. Minimum blood flow velocity (Vmin), maximum blood flow velocity (Vmax), mean blood flow velocity (Vmean), acceleration, resistive index and pulsatility index were measured in relation to the results of creatinine clearance, serum creatinine, blood urea nitrogen and 15 and 120 min values of the phenolsulfonphthalein test. RESULTS: In all patients, interlobar arteries were able to be visualized and blood-flow profile was measured. Although variations of Vmin, Vmax, Vmean and acceleration were relatively large, the resistive index and pulsatility index varied little in each kidney. Mean values of Vmin (P < 0.005), Vmean (P < 0.05), resistive index (P < 0.005) and pulsatility index (P < 0.005) were well correlated to creatinine clearance with statistical significance. CONCLUSIONS: In ADPKD, color Doppler ultrasound measurement is a useful method for assessment of renal function and could be used for monitoring the dynamic state of renal blood flow as a non-invasive technique.     

Recurrent bacteremia with enteric pathogens in recessive polycystic kidney disease

Eight children with autosomal recessive polycystic kidney disease (ARPKD) and recurrent bacteremia with enteric pathogens are described. Typical clinical features of bacterial cholangitis were absent, although in five patients histological and/or microbiological data indicated that the bacteremic episodes originated in the biliary tree. Bacteremia with enteric pathogens or recurrent culture-negative febrile illness in a child with ARPKD should raise suspicion of cholangitis, even in the absence of typical clinical findings. Received: 10 February 1999 / Revised: 15 March 1999 / Accepted: 16 March 1999     

Morbidity from Congenital Hepatic Fibrosis after Renal Transplantation for Autosomal Recessive Polycystic Kidney Disease

Presentation of autosomal recessive polycystic kidney disease (ARPKD) ranges from severe renal impairment and a high mortality rate in infancy to older children and adolescents with minimal renal disease and complications of congenital hepatic fibrosis (CHF), cholangitis and portal hypertension. Renal transplantation improves prognosis but it is unclear whether CHF in transplanted children follows the same clinical course as in older children with less severe renal disease. The aim of this study was to evaluate morbidity from CHF in ARPKD post renal transplantation. Data were analyzed for six males and eight females, transplanted for ARPKD (mean age 8.3 years, range 1-22.3 years) at the University of Minnesota between 1972 and 1998. Follow-up was for a mean of 14.5 years (range 3.1-33.6 years). One and 5 years patient survival rates were 93% and 86%, respectively. Overall five patients (36%) died; 4/5 deaths were related to CHF. Causes of death were hepatic failure immediately post transplant (n = 1), septicemia related to bile duct dilatation (n = 3) and multiorgan failure (n = 1). One and 5years graft survival rates were 87% and 70%, respectively. One patient had a combined liver-kidney transplant and two were re-transplanted. Initial signs of CHF were splenomegaly (n = 5), hepatosplenomegaly (n = 4) and gastrointestinal bleed (n = 2). Progression of CHF through childhood included hypersplenism (n = 7), esophageal varices with gastrointestinal bleeding (n = 5) and bile duct dilatation (n = 5). Portal hypertension was treated with portosystemic shunt (n = 3), sclerotherapy (n = 2), banding of varices (n = 1) and transjugular intrahepatic portosystemic shunt (n = 1). Of the nine survivors (mean age 12.8 years) 78% have functioning grafts (one liver-kidney transplant), 63% have portal hypertension and 22% have asymptomatic biliary dilatation. Complications of CHF developed in 79% of children who received a renal transplant for ARPKD. Mortality related to CHF occurred in 29% and accounted for 80% (4/5) of the deaths.     

Autosomal recessive polycystic kidney disease

The clinical features of 55 cases of autosomal recessive polycystic kidney disease (ARPCKD) have been reviewed. Each had evidence of ARPCKD. The outcomes of 87% were known; 24 had died. Twenty-four of 31 were seen between 1980 and 1986; 7 could not be traced. Forty-five percent presented under 1 month; 38% between 1 month and 1 year; and 9 cases over 1 year. Hyponatraemia occurred in 15 out of 19 aged less than 3 months; hypertension occurred in 65%; splenomegaly in 47% of those surviving more than 3 months. Portocaval shunts were done in 5 aged 2–12 years. Thirteen died of renal failure, 6 under 1 year, and 7 between 1 year and 13 years. Life-table survival rates calculated from birth revealed that 86% were alive at 3 months, 79% at 1 year, 51% at 10 years, and 46% at 15 years. Calculations based on patients who survived to 1 year of age showed that 82% were alive at 10 years and 79% at 15 years. These results reveal an improved prognosis for a condition once assumed to be fatal.Presented in part at the Xth International Congress of Nephrology, London, UK, July 1987, and at the Canadian Pediatric Society, Montreal, Canada, July 1987     

Autosomal dominant polycystic kidney disease-type 2. Ultrasound, genetic and clinical correlations.

BACKGROUND: Ultrasound, genetic and clinical correlations are available for ADPKD-1, but lacking for ADPKD-2. The present study was carried out to address: (i) the age-related diagnostic usefulness of ultrasound compared with genetic linkage studies; (ii) the age-related incidence and prevalence of relevant symptoms and complications; and (iii) the age and causes of death in patients with ADPKD-2. METHODS: Two hundred and eleven alive subjects, from three ADPKD-2 families at 50% risk, were evaluated by physical examination, consultation of hospital records, biochemical parameters, ultrasound and with genetic linkage and DNA mutation analyses. Nineteen deceased and affected family members were also included in the study. RESULTS: Of the 211 alive members, DNA linkage studies and direct mutation analyses showed that 106 were affected and 105 were not. Ultrasound indicated 94 affected, 108 not affected and nine equivocal results in nine children under the age of 15. For all ages, the false-positive diagnostic rate for ultrasound was 7.5% and the false-negative rate was 12.9%. The difference between ultrasound and DNA findings was most evident in children aged 5-14 years where the ultrasound was correct in only 50% and wrong or inconclusive in the remaining 50%. The mean age of the 106 alive, ADPKD-2 genetically affected patients was 37.9 years (range: 6-66 years). Among them, 23.5% had experienced episodes of renal pain, 22.6% were treated for hypertension, 22.6% had experienced at least one urinary tract infection, 19.8% had nephrolithiasis, 11.3% had at least one episode of haematuria, 9.4% had asymptomatic liver cysts, 7.5% had developed chronic renal failure and 0.9% had reached end-stage renal failure. Of the 19 deceased members, nine died before reaching end-stage renal failure at a mean age of 58.7 years (range: 40-68 years), mainly due to vascular complications, while the remaining 10 died on haemodialysis at a mean age of 71.4 years (range: 66-82 years). CONCLUSIONS: DNA analysis is the gold standard for the diagnosis of ADPKD-2, especially in young people. Ultrasound diagnosis is highly dependent on age. Under the age of 14, ultrasound is not recommended as a routine diagnostic procedure, but ultrasound becomes 100% reliable in excluding ADPKD-2 in family members at 50% risk, over the age of 30. ADPKD-2 represents a mild variant of polycystic kidney disease with a low prevalence of symptoms and a late onset of end-stage renal failure.     

Angiotensin-converting enzyme activity and the ACE Alu polymorphism in autosomal dominant polycystic kidney disease.

BACKGROUND: Previous studies concerning Alu I/D polymorphism in the ACE gene and ADPKD severity have used the Alu genotypes as a representative of the true biological variable, namely ACE activity. However, wide individual and ethnic differences in the proportion of variance in ACE activity explained by the I/D genotype may have confounded these studies. This investigation examines the association between ADPKD severity and ACE in terms of plasma enzyme activity and I/D genotypes in individuals from three different countries. METHODS: Blood samples were collected from 307 ADPKD patients (116 Australian, 124 Bulgarian and 67 Polish) for determination of ACE activity levels and I/D genotypes. Chronic renal failure (CRF) was present in 117 patients and end-stage renal failure (ESRF) in 68 patients. RESULTS: ACE activity was related to the I/D genotype, showing a dosage effect of the D allele (P=0.006). The proportion of variance due to the Alu polymorphism was 14%. No difference in ACE activity and I/D genotype distribution was found between patients with CRF versus normal renal function (P=0.494; P=0.576) or between those with ESRF versus those without ESRF (P=0.872; P=0.825). No effect of the I/D genotype on age at development and progression to renal failure (CRF; ESRF) was detected in the overall group, and in subgroups based on ethnic origin, linkage status and sex. CONCLUSION: ACE is not likely to play a role as a determinant of ADPKD phenotype severity.     

Autosomal dominant polycystic kidney disease associated with aortic dissection: Two case reports

We describe 2 patients with autosomal dominant polycystic kidney disease associated with aortic dissection. Both patients presented with chronic renal failure arising from autosomal dominant polycystic kidney disease, as well as with aortic dissection, DeBakey type IIIb.     

Autosomal dominant polycystic kidney disease with primary hyperaldosteronism.

We report three cases of primary aldosteronism associated with autosomal dominant polycystic kidney disease. The diagnosis of primary hyperaldosteronism was based on the presence of hypokalaemia with excessive urinary potassium excretion and/or the characteristic hormonal changes. Renal function impairment due to autosomal dominant polycystic kidney disease could mask hypokalaemia. The interpretation of adrenal imagery may be hindered by adjacent renal cysts. In one case an adrenal adenoma was detected and surgically removed, with only partial correction of the blood pressure. This could be explained by the persisting underlying autosomal dominant polycystic kidney disease. We conclude that in a hypertensive patient with polycystic kidney disease, extrarenal causes of hypertension may be present.     

Autosomal dominant polycystic kidney disease with congenital absence of contralateral kidney

Autosomal dominant polycystic kidney disease is the most frequent hereditary kidney disorder, accounting for 8–10% of the cases of end-stage renal disease. It is characterized by bilateral multiple renal cysts, nevertheless, asymmetric enlargement of the kidneys is frequently observed, and this can lead to diagnostic confusion. We report the rare occurrence of autosomal dominant polycystic disease confined to a right kidney and congenital absence of the contralateral one. Unexpected early onset of terminal renal failure in this hypertensive 23-year-old male is discussed with the review of the literature.     

Intracranial aneurysms in a child with autosomal recessive polycystic kidney disease

Intracranial aneurysms (ICA) are a well-known feature of autosomal dominant polycystic kidney disease. There is only one report about ICA in an adult patient with autosomal recessive polycystic kidney disease (ARPKD). We observed a 2-year, 6-month old girl with ARPKD and multiple ICA. The family history is negative for kidney disease. The diagnosis of ARPKD was based on the typical findings in ultrasonography and computed tomography. Cystic ectasia of biliary ducts 6.3/4.8 cm in diameter was found in the liver. Arterial hypertension in a range of 140/100–170/120 mm Hg was registered. The child has polyuria, polydipsia and enuresis. Blood urea was 15 mmol/l, creatinine in a range of 120 to 75 μmol/l. One episode of vomiting, dizziness and lethargy was the reason for a brain magnetic resonance imaging. Multiple fusiform and saccular aneurysms in the branches of middle and posterior cerebral arteries were seen bilaterally. The girl is growing well without neurological symptoms during an observation period of 1.5 years. Blood pressure is well controlled with an ACE inhibitor (Enalapril 2.5 mg daily). It was concluded that ICA can be found in patients with ARPKD. Blood pressure control is essential to reduce the risk of intracranial hemorrhage. Received: 2 May 2001 / Revised: 18 July 2001 / Accepted: 23 July 2001     

Chronic subdural haematoma and autosomal polycystic kidney disease: report of two new cases

Chronic subdural haematoma (SDH) was recently described in some patients who were suffering from autosomic dominant polycystic kidney disease (ADPKD). It results in various neurological symptoms mimicking those related to intracranial aneurysms, which are relatively frequent in such patients. The authors report two cases of chronic SDH observed in two patients known to have advanced renal failure attributed to ADPKD. Medical imaging failed to reveal features of associated intracranial abnormalities such as aneurysms or arachnoid cysts. Surgical drainage resulted in a good recovery without relapse during a long period of follow up that exceeded 10 years in the first case.