Lloyd H. Smith

L-glyceric aciduria. A new genetic variant of primary hyperoxaluria.

Abstract Four patients (three of them sibs) with recurrent calcium oxalate kidney stones excreted urinary oxalic acid and also an organic acid absent from normal urine and shown to be L-glyceric ac...

Post-traumatic renal insufficiency in military casualties. I. Clinical characteristics.

Abstract Post-traumatic renal insufficiency is important as a cause of illness and death in initially surviving combat casualties and may be seen in civilian medical practice after accidents or extensive surgery. Hypotension appears to be a primary etiologic factor although delay in therapy, inadequate blood replacement, increase in plasma hemoglobin and other pigments, and the severity of the wound may contribute to the extent of renal damage and to the hypotension itself. Impairment of renal function following trauma may be reflected in different patients by sensitive clearance tesfts only, by azotemia and decreased urinary concentrating ability, by transient oliguria or by marked oliguria of varying duration. This suggests a wide variability in the extent of functional and parenchymal renal injury. With few exceptions, only the oliguric patients develop sufficient electrolyte abnormality or clinical uremia to require special care. In the latter instances rapidly progressive potassium intoxication necessitates prompt evacuation to a treatment center and, in the patients reported here, was the major cause of death prior to the use of hemodialysis. In addition to potassium intoxication, evidence that accelerated tissue catabolism characterizes post-traumatic renal insufficiency is found in (1) rapidly developing clinical uremia with corresponding rates of NPN accumulation, (2) early signs and marked degree of weight loss and emaciation, and (3) edema formation on less than conventional fluid intake allowances. The contrast with acute renal failure of non-traumatic origin has been repeatedly emphasized. Frequently occurring extensive and progressive infection, impaired wound healing and a marked bleeding tendency in some patients complicate the clinical course and intensify the therapeutic challenge.

Disorders of oxalate metabolism.

Abstract Oxalate is a useless metabolic endproduct, formed as an unfortunate byproduct of the metabolism of glyoxylate and ascorbate. When formed it is excreted in the urine where it constitutes a hazard because of the insolubility of its calcium salt. In the majority of patients with calcium oxalate stones the urinary excretion of oxalate is normal. Reviewed herein are the acquired and genetic disorders associated with excessive oxalate excretion, in particular primary hyperoxaluria types I (glycolic aciduria) and II (glyceric aciduria). The demonstration of specific enzyme defects associated with these diseases has clarified the pathogenesis of oxalate production. Although rare, these diseases are important since they most frequently lead to early death from renal failure. Newer approaches to treatment are therefore being pursued; if successful, they might also find application in the treatment of patients with idiopathic calcium oxalate nephrolithiasis.

Post-traumatic renal insufficiency in military casualties: II. Management, use of an artificial kidney, prognosis

Abstract 1. 1. The management of fifty-one patients with post-traumatic renal insufficiency included fluid restriction, attempts to maintain caloric intake, use of cation exchange resins, the treatment of anemia and electrolyte disturbances and the use of a Brigham-Kolff artificial kidney. Interval surgical care of these patients was of great importance not only because of the severity of their wounds but particularly because of the necessity for removing necrotic and infected tissue in patients with renal failure. 2. 2. Dialysis with the artificial kidney was carried out seventy-two times in thirty-one patients of this series. It was effective in restoring clinical and chemical abnormalities toward normal and seemed to contribute to the reduction in mortality in this group of patients. 3. 3. The mortality rate accompanying acute renal failure in military casualties in Korea was approximately 80 to 90 per cent, similar to the mortality rate during World War II. After establishment of a Renal Insufficiency Center and with the use of a Brigham-Kolff type artificial kidney, the over-all mortality rate in the fifty-one patients was 53 per cent. 4. 4. The limiting factor in survival for most military patients with acute renal failure is the extent of the underlying wounds with attending infection and impaired wound healing.

Renal hyperchloremic acidosis: Familial occurrence of nephrocalcinosis with hyperchloremia and low serum bicarbonate

Abstract 1.1. A classification of the clinical features of renal acidosis is presented together with a clarification of the terms under which the disease has been described. 2.2. Two additional patients with the disease are reported. 3.3. Observations on the family of one patient are offered as the first known demonstration that this disease can exist on a familial basis. 4.4. Pathogenesis of the disease is discussed.

Hyperoxaluria in L-glyceric aciduria: possible pathogenic mechanism.

The effect of hydroxypyruvate on synthesis of oxalate and glycolate from glyoxylate was studied in in vitro preparations from normal human erythrocytes and leukocytes, rat liver, and with purified lactate dehydrogenase from beef heart. In the presence of reduced nicotinamide adenine dinucleotide, hydroxypyruvate stimulated the oxidation of glyoxylate to oxalate and decreased the reduction of glyoxylate to glycolate. These findings may explain the hyperoxaluria seen in L-glyceric aciduria (type II primary hyperoxaluria).

Inhibition of oxalate synthesis: In vitro studies using analogues of oxalate and glycolate

Abstract Fourteen analogues of oxalate or glycolate were studied as potential inhibitors of oxalate synthesis. Their inhibitory properties were determined in human erythrocytic preparations, in which the enzymatic activity seems to be predominantly, if not exclusively, lactic dehydrogenase (LDH), and in a partially purified glycolic acid oxidase preparation from rat liver. Evidence is presented that, in rat liver, nicotinamide-adenine dinucleotide (NAD)-dependent oxidation, probably catalyzed by LDH, is the major pathway for oxalate synthesis rather than flavin mononucleotide (FMN)-dependent oxidation catalyzed by glycolic acid oxidation. Of the oxalate analogues, oxalatehydrazide was found to be the most potent inhibitor of LDH-catalyzed oxalate synthesis. None of the oxalate analogues were very active as an inhibitor of glycolic acid oxidase. Hydroxymethanesulfonate was demonstrated to be a potent inhibitor of erythrocytic LDH, and the most effective compound studied for glycolic acid oxidase inhibition. Five of its structural analogues-acetoxymethanesulfonate, aminomethanesulfonate, iodomethanesulfonate, chloromethanesulfonate, and fluoromethanesulfonate—were less active in the two in vitro systems used. Other approaches to the control of oxalate synthesis are discussed. These studies furnish a background for the testing of inhibitors of oxalate synthesis in vivo .