Progress in blood pressure control in autosomal dominant polycystic kidney disease.

Hypertension occurs commonly in autosomal dominant polycystic kidney disease (ADPKD) and is an important factor in the progression of the disease and cardiovascular mortality. The aim of this prospective 15-year study is to report the rate of blood pressure control and the potential effect of a 10-point education program developed by our center for ADPKD patients and their physicians. The patients' blood pressure treatment was managed by their primary care physicians. Three 5-year periods were analyzed in which similar rates of hypertension in patients with ADPKD were present (63% to 68%). In the first period (1985 to 1989), the rate of blood pressure control (<140/90 mm Hg) was 38% for 216 hypertensive patients with ADPKD. From 1990 to 1994, the percentage of blood pressure control increased to 55% in 194 hypertensive patients with ADPKD (P < 0.001 versus 1985 to 1989); and the level of blood pressure control increased to 64% in 181 hypertensive patients with ADPKD during 1995 to 1999 (P < 0.001 versus 1985 to 1989). Although this percentage of blood pressure control in patients with ADPKD remains suboptimal, it compares very favorably with the 27% estimated blood pressure control in patients with essential hypertension from 1991 to 1994 in the United States.

Evaluation of colonic diverticular disease in autosomal dominant polycystic kidney disease without end-stage renal disease.

A previous study had shown an increased prevalence (83%) of diverticula among patients with autosomal dominant polycystic kidney disease (ADPKD) with end-stage renal disease (ESRD) compared with other ESRD patients without ADPKD (32%). Others have also suggested an increased risk for diverticular complications in renal transplant recipients with ADPKD. To determine whether there was an increased occurrence of diverticula among non-ESRD patients with ADPKD, we studied 55 patients with ADPKD who were not receiving renal replacement therapy compared with 12 unaffected family members (non-ADPKD) and 59 random patients who had undergone barium enemas (control [C]). No study patient had a history of diverticular disease. All patients underwent a double-contrast barium enema after administration of glucagon. The occurrence, number, location, and size of diverticula were noted. There was no significant difference among the three groups in regard to sex (men: ADPKD, 42% versus non-ADPKD, 42% versus C, 37%) or age (ADPKD, 49.3 +/- 0.7 versus non-ADPKD, 51.2 +/- 2.1 versus C, 49 +/- 1 years). There was no significant difference in the percentage of patients with diverticula (ADPKD, 47% versus non-ADPKD, 58% versus C, 59%), the percentage with only right-colon diverticula (ADPKD, 5% versus non-ADPKD, 17% versus C, 5%), the mean number of diverticula in patients with diverticulosis (ADPKD, 13.8 versus non-ADPKD, 7.9 versus C, 9.9 diverticula), or the size of the largest diverticula (ADPKD, 9.5 versus non-ADPKD, 10.4 versus C, 10.5 mm). There was no significant difference in these variables between the patients with ADPKD with a creatinine clearance greater than 70 mL/min/1.73 m(2) (n = 25) or less than 70 mL/min/1.73 m(2). This study does not show the greater prevalence of diverticular disease in non-ESRD patients with ADPKD compared with the general population. Thus, patients with ADPKD need not be considered at greater risk for diverticular disease than the general population.

The spectrum of autosomal dominant polycystic kidney disease in children.

The natural history of autosomal dominant polycystic kidney disease (ADPKD) has not been well described in children, and it is not known whether a relationship exists between renal structural abnormalities and function in children as has been seen in adults. Therefore, 140 children from 67 ADPKD families were studied in a prospective study. Only 22 children came with a previous diagnosis of ADPKD. In 44% of all children, at least one cyst was found on ultrasound at a mean age of 8.7 yr. Of these, 60% were classified as having moderate disease on the basis of a total cyst number of 1 to 10 cysts, whereas 40% were considered to have severe disease with a total of more than 10 cysts. There was a significant relationship between the severity of the renal structural involvement and the frequency of flank and back pain, hypertension, and impaired renal concentrating capacity. However, GFR were not reduced in children with ADPKD and did not relate to structural severity. Thirty-nine children were seen for a follow-up visit 2 to 5 yr after the initial visit. No child had progressed from nonaffected to affected with ADPKD, but three of four children with only one cyst at the time of the initial study had progressed to bilateral cysts. Among the 22 ADPKD children who had a follow-up study, there was progression of the disease, reflected by an increase in cyst number and an increase in the frequency of pain and hypertension. However, GFR remained stable in all children.(ABSTRACT TRUNCATED AT 250 WORDS)

Characteristics of very early onset autosomal dominant polycystic kidney disease.

Eleven children from eight families with autosomal dominant polycystic kidney disease who were diagnosed in utero (6 children) or in the first year of life (5 children) are reported here. Four children were evaluated for symptoms and three because of a sibling with very early onset disease. In three children, abnormal kidneys were found incidentally on a pregnancy screening ultrasound, and in only one child, the diagnosis was made by an ultrasound specifically directed at detecting polycystic kidney disease. Females were disproportionately represented among both the affected parents and offspring. Eight of the children were girls, and all affected parents were mothers. In three families, the parent's diagnosis was established only after the birth of the affected child. In two of these and in one other family, the mother's disease appeared to be the result of a new mutation. The most consistent renal ultrasonographic findings in the children were enlargement and increased echogenicity. On follow-up over 3 to 15 yr (mean, 6.8 yr) two children had ESRD and eight children had normal or nearly normal renal function as assessed by creatinine clearance. Renal concentrating ability was reduced in four children in whom it was measured. All children had bilateral renal cysts on follow-up, and nine children were hypertensive. Possible risk factors for early-onset disease identified in this study were an affected mother, an affected sibling, and an apparent parental new mutation. Symptoms and complications occurred frequently, but outcome was better than reported previously.

Clinical profiles of gross hematuria in autosomal dominant polycystic kidney disease.

There is little information on the characteristics, management, or sequelae of gross hematuria in autosomal dominant polycystic kidney disease (ADPKD). Therefore, we obtained detailed information regarding gross hematuria in 191 adult ADPKD subjects. Forty-two percent (N = 81) experienced at least one episode of gross hematuria. The mean age of the initial episode was 30 +/- 1 years; only 10% of subjects reported the first episode before age 16. Twenty-three percent of those with gross hematuria had experienced more than six occurrences. Sixty-two percent of patients with bleeding indicated a presumptive precipitating event, most commonly urinary tract infection (42% overall, 61% of females v 17% of males, P less than 0.01), or sports or strenuous activity (20% of males v 11% of females, NS). In 56% of subjects, the episode persisted for 2 to 7 days. Hypertensive ADPKD subjects were more likely to have gross hematuria than normotensive subjects (48% v 30%, P less than 0.02) and those with gross hematuria had larger renal size (820 +/- 87 v 588 +/- 52 cm3, P less than 0.03). Moreover, those subjects with more episodes of gross hematuria had a higher serum creatinine concentration than those with fewer episodes (serum creatinine: 0 episodes, 120 +/- 10 v greater than 5 episodes, 190 +/- 30 mumol/L, P less than 0.04 [1.4 +/- 0.1 v 2.1 +/- 0.3 mg/dL]). This association suggests that, although self-limited, cumulative episodes of gross hematuria may have an unfavorable impact on long-term renal function.

Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease.

Autosomal-dominant polycystic kidney disease results in renal failure at a varying age from childhood to old age. We postulated that factors other than the culprit gene alone contribute to the course of progression of the renal failure. We studied 580 subjects with autosomal-dominant polycystic kidney disease and 194 unaffected family members. We calculated survival curves to end-stage renal failure or death and developed a linear model for testing the effects of single or multiple variables on the progression of renal failure as estimated from the reciprocal of serum creatinine. Fifty-two subjects died and 94 reached end-stage renal failure during the period of observation, yielding functional survivals of 71% at age 50 years, 53% at 58 years and 23% at 70 years. The following variables were independently associated with worse mean renal function at a given age (P value less than 0.01): the PKD1 gene, younger age at diagnosis, male gender, hypertension, increased left ventricular mass, hepatic cysts in women, three or more pregnancies, gross hematuria, urinary tract infections in men and renal size expressed as renal volume. The following were not associated significantly with the course of renal function: gender of affected parent, mitral valve prolapse, intracranial aneurysms, any pregnancy, hepatic cysts in men and urinary tract infections in women. The identification of unalterable maleficent factors such as the PKD1 gene and male gender permit more informed counseling while the identification of alterable factors such as hypertension, number of pregnancies and recurrent urinary tract infections provides the clinician with the opportunity to modify these factors and improve the management of patients with autosomal-dominant polycystic kidney disease.

Renal structure and hypertension in autosomal dominant polycystic kidney disease.

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.

Risk factors for the development of hepatic cysts in autosomal dominant polycystic kidney disease.

Hepatic cysts are a major manifestation of autosomal dominant polycystic kidney disease. This study examined 239 autosomal dominant polycystic kidney disease patients and 189 unaffected family members to define the factors that influence the presence and severity of hepatic cysts. Autosomal dominant polycystic kidney disease patients with hepatic cysts were older than autosomal dominant polycystic kidney disease patients without such cysts (44.6 +/- 1.1 yr vs. 32.9 +/- 1.1 yr; p less than 0.0001). The number of hepatic cysts increased with age (r = 0.43; p less than 0.0001). Women were more likely to have massive hepatic cystic disease (greater than 15 cysts) than men (p less than 0.04). Women also had larger maximal cyst size (4.2 +/- 0.4 cm vs. 2.7 +/- 0.3 cm; p less than 0.004). Women with hepatic cysts were more likely to have been pregnant (p less than 0.001) and to have had more pregnancies (2.9 +/- 0.3 pregnancies vs. 1.6 +/- 0.2 pregnancies; p less than 0.0009). Kidney volume (p less than 0.0001), number of cysts (p less than 0.004), percentage of cystic parenchyma (p less than 0.001) and predominant cyst size (p less than 0.001) were greater and creatinine clearance was lower (64.5 +/- 3.1 ml/min/1.73 m2 vs. 94.5 +/- 3.4 ml/min/1.73 m2; p less than 0.001) in autosomal dominant polycystic kidney disease patients with hepatic cysts. By logistic regression, the frequency of hepatic cysts was related to increased age, increased severity of renal cystic disease and decreased creatinine clearance. Number and size of hepatic cysts correlated with the occurrence of pregnancy, female gender, increased age and severity of the renal lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical utility of renal concentrating capacity in polycystic kidney disease.

We studied 177 adult nonazotemic subjects with autosomal dominant polycystic kidney disease (ADPKD) and 123 unaffected family members (NADPKD). In order to assess the factors influencing renal concentrating capacity maximal urinary osmolality (UOsm) after overnight water deprivation and vasopressin was measured. UOsm was reduced in ADPKD (680 +/- 14) compared to NADPKD subjects (812 +/- 13 mOsm/kg). A greater severity of the architectural abnormality as assessed by cyst number and size and remaining volume of normal parenchyma was associated with a greater impairment of renal concentrating capacity. The concentrating defect was present in the youngest ADPKD subjects and the rate of decline of concentrating capacity with age in ADPKD paralleled that in NADPKD subjects. Based on the initial 135 subjects studied, we developed an algorithm for diagnostic screening for ADPKD utilizing blood pressure, serum creatinine and UOsm designed to maximize sensitivity. When applied to a subsequent population of 165 adults, 121 with ADPKD and 44 unaffected relatives, this algorithm would have spared 20% of unaffected subjects from the cost of ultrasound while failing to detect less than 2% of affected subjects. This simple protocol thus offers a rapid and inexpensive way to screen for ADPKD.