Mohammad Akmal

Role of parathyroid hormone in the glucose intolerance of chronic renal failure.

Evidence has accumulated suggesting that the state of secondary hyperparathyroidism and the elevated blood levels of parathyroid hormone (PTH) in uremia participate in the genesis of many uremic manifestations. The present study examined the role of PTH in glucose intolerance of chronic renal failure (CRF). Intravenous glucose tolerance tests (IVGTT) and euglycemic and hyperglycemic clamp studies were performed in dogs with CRF with (NPX) and without parathyroid glands (NPX-PTX). There were no significant differences among the plasma concentrations of electrolytes, degree of CRF, and its duration. The serum levels of PTH were elevated in NPX and undetectable in NPX-PTX. The NPX dogs displayed glucose intolerance after CRF and blood glucose concentrations during IVGTT were significantly (P less than 0.01) higher than corresponding values before CRF. In contrast, blood glucose levels after IVGTT in NPX-PTX before and after CRF were not different. K-g rate fell after CRF from 2.86 +/- 0.48 to 1.23 +/- 0.18%/min (P less than 0.01) in NPX but remained unchanged in NPX-PTX (from 2.41 +/- 0.43 to 2.86 +/- 0.86%/min) dogs. Blood insulin levels after IVGTT in NPX-PTX were more than twice higher than in NPX animals (P less than 0.01) and for any given level of blood glucose concentration, the insulin levels were higher in NPX-PTX than NPX dogs. Clamp studies showed that the total amount of glucose utilized was significantly lower (P less than 0.025) in NPX (6.64 +/- 1.13 mg/kg X min) than in NPX-PTX (10.74 +/- 1.1 mg/kg X min) dogs. The early, late, and total insulin responses were significantly (P less than 0.025) greater in the NPX-PTX than NPX animals. The values for the total response were 143 +/- 28 vs. 71 +/- 10 microU/ml, P less than 0.01. There was no significant difference in the ratio of glucose metabolized to the total insulin response, a measure of tissue sensitivity to insulin, between the two groups. The glucose metabolized to total insulin response ratio in NPX (5.12 +/- 0.76 mg/kg X min per microU/ml) and NPX-PTX (5.18 +/- 0.57 mg/kg X min per microU/ml) dogs was not different but significantly (P less than 0.01) lower than in normal animals (9.98 +/- 1.26 mg/kg X min per microU/ml). The metabolic clearance rate of insulin was significantly (P less than 0.02) reduced in both NPX (12.1 +/- 0.7 ml/kg X min) and NPX-PTX (12.1 +/- 0.9 ml/kg X min) dogs, as compared with normal animals (17.4 +/- 1.8 ml/kg X min). The basal hepatic glucose production was similar in both groups of animals and nor different from normal dogs; both the time course and the magnitude of suppression of hepatic glucose production by insulin were similar in both in groups. There were no differences in the binding affinity, binding sites concentration, and binding capacity of monocytes to insulin among NPX, NPX-PTX, and normal dogs. The data show that (a) glucose intolerance does not develop with CRF in the absence of PTH, (b) PTH does not affect metabolic clearance of insulin or tissue resistance to insulin in CRF, and (c) the normalization of metabolism in CRF in the absence of PTH is due to increased insulin secretion. The results indicate that excess PTH in CRF interferes with the ability of the beta-cells to augment insulin secretion appropriately in response to the insulin-resistant state.

Renal Involvement in Mixed Connective Tissue Disease: A Longitudinal Clinicopathologic Study

Eleven of 30 patients with MCTD, followed for a mean of 10 years, developed immune complex nephropathy (five membranous, two mesangial, one mixed, and one sclerosing) with NS in nine of 11. Another patient had membranous nephropathy at autopsy. Patients with renal disease tended to have more systemic manifestations than those without. NS was at times of abrupt onset, recurrent, and/or persistent. Anti-RNP and serum complement were not helpful in predicting nephritis. Seventy-two percent of nephropathy and 62% of NS episodes resolved or improved after corticosteroid therapy. Five patients became hypertensive, two developed chronic renal failure and required chronic dialysis, and one needed acute dialysis twice. One patient progressed to focal proliferative crescentic nephritis with necrotizing arteritis. Three patients with nephropathy died, two of pulmonary hypertension with acute cor pulmonale and one of overwhelming sepsis. Nephropathy is relatively common in MCTD, is associated with substantial morbidity, and with the risk of hypertension and chronic renal failure.

Resolution of Muscle Calcification in Rhabdomyolysis and Acute Renal Failure

We studied four patients with acute renal failure associated with nontraumatic rhabdomyolysis to evaluate the presence and progression of calcium deposits in damaged muscle tissue. Conventional and electron radiography and technetium-99m diphosphonate (TcDP) scans were done during the oliguric phase of acute renal failure and repeated after renal function returned to normal. Three patients showed deposits of calcium by conventional radiography and all by electron radiography and TcDP during the oliguric period. When the patients recovered renal function and muscle injuries healed, calcium deposits disappeared. The results show that calcium deposits in damaged muscle occur during the oliguric phase of acute renal failure due to rhabdomyolysis and the calcification disappears with recovery of renal failure; and TcDP scans are the most sensitive method of detecting calcium deposits in these patients.

Rhabdomyolysis with and without Acute Renal Failure in Patients with Phencyclidine Intoxication

Rhabdomyolysis occurred in 25 of 1,000 patients (2.5%) with phencyclidine (PCP) intoxication. 10 of these 25 patients (40%) developed acute renal failure and another 7 had mild impairment in renal function. Marked hyperuricemia was present in all 17 patients, and marked hyperphosphatemia and hypocalcemia were noted in the 10 patients with acute renal failure; 3 of the latter developed hypercalcemia during the diuretic phase of the illness. Fever, tachycardia and hypertension were frequent findings among the 25 patients with rhabdomyolysis and all had leukocytosis. The data show that rhabdomyolysis with and without acute renal failure is not infrequent among abusers of PCP.

Reversible hepatic dysfunction associated with rhabdomyolysis

Hepatic dysfunction was observed in 34 patients with nontraumatic rhabdomyolysis. The serum levels of lactic dehydrogenase were markedly elevated in all patients. The peak values occurred within 72 h of hospitalization. There was no significant difference among patients with (9,044 +/- 1,154 U/l) and without acute renal failure (ARF; 9,125 +/- 3,067 U/l). Similarly, marked elevation in both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed within 72 h after admission to the hospital. They were significantly higher in patients with ARF (ALT: 4,718 +/- 785 vs. 2,496 +/- 927 U/l, p less than 0.01; AST: 3,635 +/- 820 vs. 1,352 +/- 624 U/l, p less than 0.01). Hyperbilirubinemia was noted in 13 of 22 (60%) patients with ARF and in 5 of the 12 (41%) of those without ARF. Serum levels of bilirubin ranged from 2.6 to 14.3 mg/dl. Prothrombin time was prolonged in 4 of 12 (33%) without ARF and in 14 of 22 (63%) of patients with ARF. This abnormality lasted from 1 to 13 days. The magnitude and duration of hyperbilirubinemia and abnormal prothrombin time were similar in patients with and without ARF. Hepatic dysfunction appears to occur in about 25% of patients with rhabdomyolysis. The pathogenesis of these abnormalities is not well defined and may be multifactorial. Hyperpyrexia, hypotension and proteases released from injured muscle may each or all be contributory. These hepatic derangements are reversible.

Verapamil prevents chronic renal failure-induced abnormalities in lipid metabolism.

Hypertriglyceridemia is common in chronic renal failure (CRF); this derangement is due to decreased peripheral removal of triglycerides. Certain data indicate that the state of secondary hyperparathyroidism of CRF is, at least in part, responsible for derangements in lipid metabolism. It has been proposed that chronic excess of parathyroid hormone exerts its deleterious effects on many organs through its ability to raise basal levels of cytosolic calcium. Prevention of the latter by a calcium channel blocker is followed by the correction of organ dysfunctions. The present study examined the effect of treatment of CRF rats with verapamil on several parameters of lipid metabolism. Chronic renal failure rats displayed hypertriglyceridemia, fat intolerance, reduced postheparin plasma lipoprotein and hepatic lipase activities, decreased hepatic lipase in liver homogenate, and elevated calcium content in liver and epididymal fat. Treatment of the CRF rats with verapamil prevented all these derangements in lipid metabolism. These effects of verapamil were similar to those produced by parathyroidectomy of CRF rats. The data are consistent with the formulation that chronic excess of parathyroid hormone increases the calcium burden of liver and adipose tissue and consequently impairs the synthesis and/or release of lipoprotein and hepatic lipases. Reduced availability of these enzymes in plasma results in impared peripheral removal of triglycerides, leading to hypertriglyceridemia.

Erythrocyte survival in chronic renal failure. Role of secondary hyperparathyroidism.

The human erythrocyte (RBC) is a target organ for parathyroid hormone (PTH) and the hormone increases RBC osmotic fragility and induces their hemolysis. The present study was undertaken to examine whether elevated blood levels of PTH affect RBC survival, and therefore whether PTH, being an extracorpuscular factor, is responsible for the shortened RBC survival in chronic renal failure. 51Cr-labeled RBC survival was elevated in six normal dogs, in six animals with chronic renal failure and secondary hyperparathyroidism (NPX), and in six thyroparathyroidectomized dogs (NPX-TPTX) with comparable degree and duration of chronic renal failure. In the normal dogs, 51Cr-labeled RBC survival ranged between 22 and 35 (25.6 +/- 1.9) d. In the NPX dogs, 51Cr-labeled RBC survival was shortened and the values ranged between 16 and 20 (18.4 +/- 0.6) d, a value significantly (P less than 0.01) lower than normal dogs. In NPX-TPTX dogs, 51Cr-labeled RBC survival ranged between 20 and 33 (25.2 +/- 1.8) d, a value not different from that in normal dogs but significantly higher (P less than 0.01) than that in NPX animals. Our data demonstrate that excess blood levels of PTH and not other consequences of the uremic state are responsible for the shortened RBC survival in chronic renal failure.

Rhabdomyolysis in a Patient with Hypocalcemia due to Hypoparathyroidism

The purpose of this report is to present a case of rhabdomyolysis associated with hypocalcemia due to idiopathic hypoparathyroidism. Throughout hospitalization and 1 year of outpatient follow-up, this patient displayed an inverse relationship between serum creatine phosphokinase and lactic dehydrogenase levels, and serum calcium levels.

Compression of the left brachiocephalic vein by the innominate artery resulting in massive arm edema in a hemodialysis patient.

We report case of extrinsic compression of the left brachiocephalic vein by the innominate resulting in massive edema of the arm in a patient with hemodialysis Gore-Tex graft. To our knowledge, such phenomenon has not been previously reported.

Parathyroid Hormone Interferes with Extrarenal Disposition of Potassium in Chronic Renal Failure

Available data suggest that the permeability of cellular membranes to potassium is affected by cytosolic calcium. Parathyroid hormone (PTH) has a calcium ionophoric property; it enhances calcium entry into many cells and it increases calcium content in a variety of tissues. Therefore, it is possible that clinical states with excess PTH may affect potassium homeostasis. The present study examined the effect of secondary hyperparathyroidism of chronic renal failure (CFR) on extrarenal potassium disposition of intravenous KCl load in rats with CRF. Experiments were performed after 21-26 days of CRF produced by 7/8 nephrectomy in rats with intact parathyroid glands (CRF control), in normocalcemic parathyroidectomized CRF animals (CFR-PTX) and in adrenalectomized CRF rats (CRF-ADX) maintained with DOCA. The effects of treatment with calcium channel blocker, verapamil, and of PTH administration were also examined. The baseline plasma concentrations of potassium in CRF-PTX rats and in CRF control animals treated with verapamil were significantly (p less than 0.01) lower than those with CRF control and CRF-ADX rats. At the end of 90 min of KCl infusion, the plasma concentrations of potassium as well as the changes from baseline were significantly (p less than 0.01) higher in CRF animals with secondary hyperparathyroidism (CRF control and CRF-ADX) and in those treated with PTH (CRF control with PTH and CRF-PTX with PTH) than in those without secondary hyperparathyroidism CRF-PTX and in those with secondary hyperparathyroidism but treated with verapamil (CRF control with verapamil and CRF-ADX with verapamil).(ABSTRACT TRUNCATED AT 250 WORDS)