"U" curve association of blood pressure and mortality in hemodialysis patients. Medical Directors of Dialysis Clinic, Inc.

BACKGROUND: Hypertension may play an important role in the pathogenesis of the excess cardiovascular and cerebrovascular (CV) morbidity observed in hemodialysis patients (HD). However, the optimal blood pressure (BP) range for HD patients has not been defined. We postulated that there is a "U" curve relationship between BP and CV mortality. To explore this hypothesis we studied 5,433 HD patients in Dialysis Clinic Inc., a large not-for-profit chain, over a five year period. METHODS: Cox regression, with fixed and time-varying covariates, was used to assess the effect of systolic blood pressure (SBP) and diastolic blood pressure (DBP), pre- and post-dialysis, on CV mortality, while adjusting for age, gender, ethnicity, primary cause of end-stage renal disease, Kt/V, serum albumin, and antihypertensive medications. RESULTS: The overall impact of BP on CV mortality was modest. Pre-dialysis, neither systolic nor diastolic hypertension were associated with an increase in CV mortality. Post-dialysis, SBP > or = 180 mm Hg (RR = 1.96, P < 0.015) and DBP > or = 90 mm Hg (RR = 1.73, P < 0.05) were associated with increased CV mortality. Low SBP (SBP < 110 mm Hg) was associated with increased CV mortality, pre- and post-dialysis. CONCLUSIONS: The results suggest the presence of a "U" curve relationship between SBP post-dialysis and CV mortality in HD patients.

Dissociative effects of piretanide on proximal tubular PO4 and HCO3 transport.

The effect of piretanide on renal electrolyte transport was evaluated by simultaneous micropuncture and clearance studies. In chronically thyroparathyroidectomized (TPTX) dogs, the drug caused an increased percentage excretion (%E) of sodium (from 0.6 +/- 0.1 to 15.2 +/= 1.8%, P less than 0.01) as well as of calcium (from 1.0 +/- 0.2 to 17.8 +/- 1.7%, P less than 0.001) and bicarbonate (from 1.2 +/- 0.4 to 5.9 +/- 0.9, P less than 0.001), but there was no change in %E of phosphate (4.0 +/- 0.9 to 6.6 +/- 1.6, P less than 0.10). In the presence of a constant infusion of parathyroid hormone (PTH) the drug caused a greater degree of natriuresis, calciuria, and bicarbonaturia and a significant increase in %E of PO4 (from 7.4 +/- 1.6 to 20.0 +/- 2.1, P less than 0.05). Proximal fractional reabsorption (PFR) of PO4 was unaffected, but there was a significant decrease in PFR of sodium, calcium, and bicarbonate in the TPTX dogs. The presence of PTH did not alter the effects of piretanide on PFR of phosphate and bicarbonate. There was no change in urinary or tubular fluid pH in either group of dogs. These data indicate that piretanide dissociates proximal PO4 transport from that of sodium and bicarbonate. In the presence of PTH, the drug inhibits PO4 transport beyond the late proximal convoluted tubule. In addition, tubular (and urinary) pH appears to be an important regulator of PO4 transport, especially in the absence of PTH.

Therapy of renal osteodystrophy with dihydrotachysterol in non-dialyzed patients.

Two non-dialyzed patients with severe uremic bone disease were treated successfully with dihydrotachysterol (DHT). In each case, dramatic clinical improvement was noted in several weeks and this was verified by biochemical, radiologic and histologic measurements. Although DHT has been utilized previously in combination with dialysis, its documented effectiveness in the absence of the latter therapy has not previously been reported.

Mechanism of the phosphaturia due to chlorothiazide.

CTZ caused a phosphaturia when baseline phosphate excretion was not already high. Furthermore, when th influence of PTH is withdrawn, the excretion of phosphate appears to be largely affected by changes in urinary pH.

Diabetic nephropathy as the mode of presentation of diabetes mellitus.

Diabetic nephropathy have only rarely been described in patients who have minimal or no glucose intolerance. We herein report the case of a 59-yr-old man who presented with nephrotic syndrome and minimal glucose intolerance whose renal biopsy showed the nodular (Kimmelsteil-Wilson) and diffuse glomerulosclerosis lesions characteristic of diabetes. We critically review the literature on this subject, pointing out the pitfalls in diagnosis and establishing strict criteria for the diagnosis of diabetic nephropathy in patients wihout overt clinical diabetes.

Acute effects of piretanide in normal subjects.

Acute clearance studies were performed in normal subjects to assess the actions of the new diuretic, piretanide, on renal function. The drug increased both glomerular filtration rate and effective renal plasma flow in roughly proportionate amounts, so that filtration fraction did not change. In a dosage of 2 to 3 mg, it induced an increase in sodium excretion of almost 13% of filtered load, and there was an associated 2- to 3-fold increase in potassium excretion. The abstraction of solute-free water from the collecting duct was markedly reduced, but the drug induced no significant decline in the generation of free water. The rate of bicarbonate excretion, as well as that of titratable acid and ammonium, was increased approximately proportionately so that there was no increase in urinary pH or net hydrogen ion excretion. There was no phosphaturia, a unique finding, since all other drugs and maneuvers that cause a bicarbonate diuresis are also phosphaturic. Piretanide increased calcium excretion by approximately 19% of filtered load. The data suggest that the drug acts largely in the ascending limb of the loop of Henle and that it also affects the proximal tubule. Despite its sulfonamide structure, none of the drug's effects appear to be related to inhibition of carbonic anhydrase.

Uncoupling of proximal sodium bicarbonate from sodium phosphate transport by bumetanide.

Re-collection micropuncture of late proximal tubular segments and simultaneous clearance studies were performed in chronically thyroparathyroidectomized dogs before and after the intravenous administration of bumetanide. The drug, a new sulfonamide-derivative diuretic, inhibited proximal fractional sodium and fluid transport by 0.12 (from 0.44 +/- 0.04 to 0.32 +/- 0.04, P less than 0.05) and that of bicarbonate by 0.14 (from 0.43 +/- 0.05 to 0.29 +/- 0.07, P less than 0.02). Tubular fluid bicarbonate concentration was unchanged, indicating a reduction in the transport of this ion proportionate to that of tubular fluid. However, unlike sodium and bicarbonate reabsorption, fractional proximal phosphate transport was unaltered (from 0.65 +/- 0.04 to 0.62 +/- 0.04, P greater than 0.40). The drug induced a substantial natriuresis; the percentage of filtered sodium excreted rose from 0.4 +/- 0.1 to 13.1 +/- 2.4% (P less than 0.005). Bicarbonate and phosphate excretion rose more modestly: the percentage excretion of the former ion increased from 0.9 +/- 0.3 to 3.7 +/- 0.08% (P less than 0.005) and that for phosphate doubled (from 3.4 +/- 1.0 to 6.8 +/- 1.3%, P less than 0.025). However, urinary pH did not change. Accordingly, bumetanide uncoupled the transport of sodium bicarbonate from that of sodium phosphate in the proximal convoluted tubule. It is concluded from these data that the action of bumetanide in the proximal convoluted tubule is probably not related either to carbonic anhydrase inhibition or to the impairment of sodium-phosphate-linked transport.