A young adult (approximately 20 months), 125 g, female degu (Octodon degus) was housed with a male degu for approximately 1.2 years as a breeding pair. The female was multiparous and had weaned its third litter 2 weeks earlier. The degu was reported to the veterinary service for bloody vaginal discharge and a hunched, thin appearance of 1 day's duration. On physical examination, it exhibited cachexia, molting, slight matting of the hair around the eyes, and moderate dehydration. Hematology results included anemia and leukopenia with lymphocytopenia. Biochemical abnormalities included severe azotemia and phosphatemia. Urine specific gravity was 1.016. The condition of this animal prohibited its continued use in the breeding colony, so it was submitted for necropsy. On gross examination, the left kidney measured 10 x 15 mm, had an irregular surface, and was pale and mildly enlarged, consistent with compensatory hypertrophy. The right kidney was small (5 x 8 mm) and cystic. Both adrenal glands appeared mildly enlarged. Histologically, the left kidney had multiple regions with chronic, diffuse interstitial nephritis, and the right kidney was polycystic. There was mild, focal, cortical nodular hyperplasia in the adrenal glands. In the uterus, there was unilateral, locally extensive necrosis of the endometrium. The clinical chemistry results and histopathology findings are supportive of a diagnosis of renal failure secondary to chronic nephritis and polycystic kidney disease. The etiology of the nephritis is unknown. Polycystic kidney disease can be congenital or hereditary in other rodents.

BACKGROUND AND METHODS. Intracranial aneurysms are a feature of autosomal dominant polycystic kidney disease, but their prevalence is uncertain. We studied 92 subjects with autosomal dominant polycystic kidney disease who had no symptoms or signs of any neurologic disorder. To determine the prevalence of intracranial aneurysms, we performed high-resolution computed tomography (CT) in 60 subjects, four-vessel cerebral angiography in 21, and both procedures in 11. RESULTS. Four of the 88 subjects in whom the radiologic studies were successfully completed had intracranial aneurysms (4 percent; 95 percent confidence interval, 0.1 to 9 percent), as compared with the prevalence of 1 percent reported for an angiographic study of the general population. Three of the four subjects had multiple aneurysms. Seven subjects for whom the results of CT studies were suspicious underwent cerebral angiography: two had aneurysms, and five had normal vascular structures that accounted for the suspicious results of tomography. Four subjects who had normal CT imaging studies also had normal angiographic examinations. Eight of the 32 subjects who underwent angiography (25 percent) had transient complications, as compared with 22 of 220 control subjects (10 percent) who did not have polycystic kidney disease (P less than 0.05). We could not identify any risk factor in these subjects that was related to the occurrence of aneurysm. CONCLUSIONS. Asymptomatic intracranial aneurysms appear to be more frequent in people with polycystic kidney disease than in the general population, although our 95 percent confidence interval includes the possibility of no difference. Because cerebral angiography is associated with increased morbidity in people with polycystic kidney disease, we recommend high-resolution CT as a screening test.

To develop a profile of nonazotemic polycystic kidney disease as it occurs in families, we identified and studied 164 persons with autosomal-dominant polycystic kidney disease, 81 persons suspected of having the disease, and 250 family members without the disease. Because symptoms were absent in 32% of patients with the disease but present in 30% of persons without the disease, symptoms are not reliable in screening for the disease. Hypertension and palpable kidneys and liver were significantly commoner in patients with the disease, but systolic murmur unrelated to hypertension (10.5%) and peripheral edema (9.3%) also were common. Normal laboratory values do not exclude the diagnosis of polycystic kidney disease. Ultrasonography appears to be more sensitive than excretory urography in detecting the disease and also can detect hepatic cysts. Berry aneurysms can occur and are an important cause of mortality and morbidity. The relation of renal cysts to signs, symptoms and renal function is discussed.

Hypertension has been reported to occur in 50 to 75 percent of subjects with autosomal dominant polycystic kidney disease (ADPKD) prior to the onset of marked renal insufficiency but concurrent with cystic deformation of the renal parenchyma. The present study was undertaken to examine whether the renal structural abnormalities are greater in hypertensive (HBP) versus normotensive (NBP) male and female patients with ADPKD who were matched within gender groups for age, body surface area, serum creatinine concentration (males HBP 1.2 +/- 0.02 vs. NBP 1.1 +/- 0.03 mg/dl. NS: females HBP 0.9 +/- 0.03 vs. NBP 0.9 +/- 0.02 mg/dl, NS) and creatinine clearance (males HBP 100 +/- 3 vs. NBP 108 +/- 3 ml/min/1.73 m2, NS: females HBP 97 +/- 3 vs. NBP 96 +/- 2 ml/min/1.73 m2, NS). Renal volume was significantly greater in the HBP compared to the NBP group (males HBP 624 +/- 47 vs. NBP 390 +/- 43 cm3, P less than 0.0005; females HBP 446 +/- 32 vs. NBP 338 +/- 24 cm3, P less than 0.002). Since increased renal volume is due to increased cysts, the results indicate that the early high incidence of hypertension in ADPKD correlates with the renal structural abnormalities in this disorder.

A high level of polycystin-1 expression is detected in kidneys of all patients with autosomal dominant polycystic kidney disease (ADPKD). Mice that overexpress polycystin-1 also develop renal cysts. Whether overexpression of polycystin-1 is necessary for cyst formation is still unclear. Here, we report the generation of a targeted mouse mutant with a null mutation in Pkd1 and its phenotypic characterization in comparison with the del34 mutants that carry a 'truncation mutation' in Pkd1. We show that null homozygotes develop the same, but more aggressive, renal and pancreatic cystic disease as del34/del34. Moreover, we report that both homozygous mutants develop polyhydramnios, hydrops fetalis, spina bifida occulta and osteochondrodysplasia. Heterozygotes also develop adult-onset pancreatic disease. We show further that del34 homozygotes continue to produce mutant polycystin-1, thereby providing a possible explanation for increased immunoreactive polycystin-1 in ADPKD cyst epithelia in the context of the two-hit model. Our data demonstrate for the first time that loss of polycystin-1 leads to cyst formation and defective skeletogenesis, and indicate that polycystin-1 is critical in both epithelium and chondrocyte development.

Twelve patients with chronic renal failure and polycystic kidney disease represent 8% of the 151 hemodialysis patients followed up at the Chromalloy American Kidney Center, Washington University School of Medicine. Ten (83%) of these patients have diverticulosis, and four of these patients developed gross colonic perforation secondary to diverticulitis. Barium enemas on 31 chronic renal failure patients without polycystic kidney disease revealed diverticulosis in 10 (32%). None had diverticulitis. Barium enemas in 120 age-matched non-renal failure control patients revealed diverticulosis in 45 (38%). None had diverticulitis. These findings suggest that patients with chronic renal failure due to polycystic kidney disease have a high incidence of diverticulosis and diverticulitis, that diverticulosis occurs in patients with chronic renal failure without polycystic kidney disease at a rate similar to that in the general population, and that diverticulitis should be an initial consideration in the differential diagnosis of abdominal pain in patients with polycystic kidney disease.

The rate of progression of early renal failure was evaluated in three groups of adult patients with renal disease of diverse etiology on dietary protein and phosphorus restriction (about 0.6 g/kg of protein, 700 mg of phosphorus) and in a control group of 22 patients with the same renal disease, retrospectively studied, on a free diet. Group 1 had 33 patients with chronic glomerulonephritis (CG), initial serum creatinine (Scr) of 1.4 to 4.3 mg/dl (mean, 2.20), followed for 5 to 94 months (mean, 44). Group 2 had 17 patients with polycystic kidney disease (PKD), Scr 1.3 to 4.7 mg/dl (mean, 2.40), followed for 8 to 81 months (mean, 42). Group 3 had 28 patients with primary chronic pyelonephritis (CP), Scr of 1.5 to 4.5 mg/dl (mean, 2.57), followed for 9 to 92 months (mean, 41). The control group had 22 patients (11 with CG, five with PKD, and six with CP), with Scr 1.7 to 4.1 mg/dl, followed for 6 to 72 months (mean, 24). In the regression analysis between reciprocal creatinine and time, the slopes were -0.0017,-0.0025, and -0.00016 dl/mg/month in the three patient groups on a protein-restricted diet, respectively. The difference between both groups 1 and 2 and group 3 was statistically significant (P less than 0.05). The slopes in patients on a free diet were significantly greater than those found in patients on a protein-restricted diet. The actuarial survival probability at 72 months, assuming as "renal death" a Scr of 10 mg/dl, was 45% in patients with CG, 44% in those with PKD, and 67% in those with CP on a protein-restricted diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertension is common in patients with polycystic kidney disease (PKD). This study addresses the hypothesis that sympathetic activity is enhanced in hypertensive PKD patients, not only when renal function is impaired but also when renal function is still normal. Muscle sympathetic nerve activity (MSNA, peroneal nerve), plasma renin activity (PRA), heart rate, and BP were studied in PKD patients with normal and with impaired renal function and in matched controls. In hypertensive patients with normal renal function, MSNA and mean arterial pressure (MAP) were higher than in normotensive patients (23 +/- 5 versus 15 +/- 7 bursts/min; 110 +/- 10 versus 90 +/- 3 mmHg; P < 0.05), whereas PRA and heart rate did not differ. In PKD with chronic renal failure (CRF)(creatinine clearance rate, 39 +/- 19 ml/min), MAP, MSNA and PRA were higher than in controls (resp, 116 +/- 7 versus 89 +/- 9 mmHg; 34 +/- 14 versus 19 +/- 9 bursts/min; 405 [20 to 1640] versus 120 [40 to 730] fmol/L per sec; all P < 0.05). Heart rate in PKD CRF did not differ from controls. MSNA correlated with MAP (r = 0.42; P = 0.01) and age with MSNA (r = 0.45; P < 0.01). Regression line of age and MSNA in patients was steeper than that in controls. This study indicates that MSNA is increased in hypertensive PKD patients regardless of renal function. The data support the idea that sympathetic hyperactivity contributes to the pathogenesis of hypertension in PKD.

As many as 1% of newborn infants have a prenatal diagnosis of hydronephrosis or significant renal pelvic dilation. Hydronephrosis often is caused by nonobstructive conditions. The likelihood of significant urologic pathology is directly related to the size of the fetal renal pelvis, and 90% with an anteroposterior diameter more than 2 cm need surgery or long-term urologic medical care. Following delivery, antibiotic prophylaxis should be administered and a renal sonogram and voiding cystourethrogram should be obtained. If there is grade 3 or 4 hydronephrosis, usually a diuretic renogram is recommended also. Pediatric urologic or pediatric nephrologic consultation usually is helpful in planing evaluation and treatment. Prenatal recognition of hydronephrosis allows neonatal diagnosis and treatment of urologic pathology, preventing complications of pyelonephritis and obstruction.

Patients with polycystic kidney disease are at increased risk of subarachnoid hemorrhage from rupture of intracranial aneurysms. We used decision analysis to assess whether or not patients with polycystic kidney disease should undergo routine cerebral arteriography for intracranial aneurysms and prophylactic surgery, if an aneurysm is detected. We incorporated published data on the prevalence of intracranial aneurysms in patients with polycystic kidney disease, the annual rate of aneurysmal rupture, the risk of grave complications of rupture, and the likelihood of grave complications of arteriography and prophylactic surgery. Outcomes were assessed as years of survival, and benefit was calculated as the gain in survival. Our analysis shows that arteriography should not be carried out routinely because its benefit exceeds one year only if the prevalence of aneurysm exceeds 30 per cent, if the surgical complication rate is 1 per cent or less, and if the patient is under 25 years of age. If newer noninvasive tests, such as digital-subtraction angiography, prove to identify reliably patients who are highly likely to have a cerebral aneurysm, routine screening with these tests will be warranted in patients with polycystic kidney disease.