Normotensive Autosomal Dominant Polycystic Kidney Disease Patients Research Articles

Microalbuminuria in normotensive patients with autosomal-dominant polycystic kidney disease.

Microalbuminuria (MA) is present in hypertensive autosomal-dominant polycystic kidney disease (ADPKD) patients, but has not been reported in normotensive ADPKD patients. We examined the prevalence of MA and the effect of different determinants on urinary albumin excretion in a group of 42 normotensive ADPKD patients. Metabolic parameters, plasma renin activity and aldosterone and serum angiotensin-converting enzyme (ACE) activity were determined. A 24-h urine sample two or three times over a 6-month period was collected to evaluate MA. Each patient underwent an echocardiography to measure left ventricular mass. Eight patients (19%) showed MA (61.6 mg/day, range 37-164), whereas 34 patients (81%) were normoalbuminuric (8.8 mg/day, range 2-29). The groups were matched for all possible confounding variables, but microalbuminuric patients showed a tendency towards greater systolic blood pressure, plasma renin activity and left ventricular mass. There was no correlation between MA and age, sex, body mass index, systolic or diastolic blood pressure, plasma renin activity, serum ACE levels or left ventricular index. The present study demonstrates a high prevalence of MA in normotensive ADPKD patients. MA may be a predictor of early renal and vascular damage in these patients.

Left ventricular hypertrophy in autosomal dominant polycystic kidney disease.

Cardiovascular complications are the most common cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). To understand this relationship, known cardiovascular risk factors were examined in ADPKD. Left ventricular hypertrophy (LVH) is a known, important risk factor for premature cardiovascular death in patients with essential hypertension. Hypertension is known to occur frequently and early in ADPKD patients. The frequency of LVH in ADPKD patients and its relation with hypertension and other risk factors, however, is not known. In this study, echocardiographic tests were performed in 116 consecutive adult ADPKD patients and 77 healthy control subjects. There was a significantly higher frequency of LVH in ADPKD men (46 versus 20%, P < 0.05) and women (37 versus 12%, P < 0.005) compared with control subjects. LVH in ADPKD patients was associated with higher systolic and diastolic arterial BP. There also was an association between LVH, diminished renal function, and increased renal volume. When comparing ADPKD patients with and without LVH, the former were older, weighed more, had a higher prevalence of hypertension, and had a lower hematocrit value and more renal impairment. LVH was also present in 23% of normotensive ADPKD patients and 16% of healthy control subjects (P = NS), but did not correlate with BP. The role of BP as a contributing factor to LVH in ADPKD patients may be due in part to earlier onset and inadequate treatment.

Autosomal dominant polycystic kidney disease (ADPKD)--mechanisms of cyst formation and renal failure.

None of the hypotheses proposed so far to explain cyst formation in autosomal dominant polycystic kidney disease (ADPKD) is entirely satisfactory, e.g. the theory of tubular obstruction by intraluminal polyps or dilatation of nephron segments as a consequence of abnormal compliance of the basement membrane. Recent in vitro studies show that (i) synthesis of basement membrane material is abnormal and that (ii) the direction of transepithelial resorptive flux into a secretory mode is reversed as a consequence of faulty insertion of Na, K-ATP'ase into the luminal membrane. It remains unclear why cystic transformation of a few percent of nephrons should cause endstage renal failure. Our clinical and experimental studies do not provide evidence to support some hypotheses proposed in the past, i.e. that renal parenchyma is compressed by expanding cysts and that glomeruli are overperfused. Our histological studies show that progression to endstage renal failure is associated with (i) progressive arteriolar lesions (out of proportion to the vascular lesions seen in extrarenal vascular beds; and (ii) progressive interstitial fibrosis. It appears that fibroblasts in ADPKD are particularly sensitive to platelet derived growth factor (PDGF) which is secreted by epithelial cells of the cyst wall in a paracrine fashion. In contrast to previous opinion, which was presumably skewed by ascertainment bias, it appears that not all, and perhaps not even a majority, of ADPKD patients progress to endstage renal failure. Factors related to progression are gender, family history and hypertension. Both abnormal sodium excretion and inappropriate renin secretion play a role in the genesis of hypertension. Elevated blood pressure, albeit within the normotensive range, is demonstrable even in prepubertal children. The involvement of renin in renal vasoconstriction of normotensive ADPKD patients suggests a particular role of ACE inhibitors in the management of these patients.