Garabed Eknoyan

Plasma Acid-Base Patterns in Diabetic Ketoacidosis

In a study of the types of plasma acid-base patterns present at 196 admissions for diabetic ketoacidosis we found no relation between the initial level of serum total carbon dioxide and the plasma anion gap; instead, there was a broad spectrum of acid-base patterns, ranging from pure anion-gap acidosis to pure hyperchloremic acidosis. Although the degree of renal dysfunction on admission, which reflected the magnitude of volume depletion, was independent of the severity of metabolic acidosis, it was responsible for the variable retention of plasma ketones: the more severe the volume depletion on admission, the greater the ketone retention and the less prominent the hyperchloremic acidosis. Recovery from acidosis was significantly slower in patients admitted with pure hyperchloremic acidosis. After therapy, hyperchloremia developed in most patients at four to eight hours after admission, because of the retention of chloride in excess of sodium and the excretion of ketones by the kidney.

Localization of diuretic action from the pattern of water and electrolyte excretion.

The response to diuretic agents is principally determined by three factors: the locus in the nephron where the drug exerts its inhibitory effect on sodium reabsorption; the potency of its action; and the nature and magnitude of the internal regulatory influences which augment the renal tubular reabsorption of sodium. The present studies in dogs were undertaken to ascertain the site of action within the nephron of various diuretic agents. The site of action was inferred from the pattern of water and electrolyte excretion during water diuresis and hydropenia. In general, the following criteria were used: An action in the proximal tubule was assumed if the fraction of filtrate delivered out of this portion of the nephron after administration of a diuretic (as estimated from clearance studies) exceeded that normally delivered out of the proximal convolution (as disclosed by micropuncture studies). An action in the ascending limb of Henle’s loop was assumed if free-water clearance was impaired, either alone or together with an impairment of free-water reabsorption. Finally, an action in the distal tubule and collecting duct was assumed if potassium and hydrogen excretion was reduced at any given rate of sodium excretion. Micropuncture studies in dogs, utilizing the inulin tubular fluid to plasma ratio (inulin TF/P) at the end of the proximal convolution as an index of fractional reabsorption of the filtrate, have delineated the magnitude of sodium reabsorption in this portion of the nephron during normal circumstances and during water diuresis, saline diuresis, and contraction of effective blood volume.13 No similar characterization of reabsorption in the thick ascending limb is available, since micropuncture has not been applicable in the dog to this segment of the nephron. It was necessary, therefore, to examine the normal reabsorptive characteristics of the thick ascending limb as a function of delivery of filtrate before the effects of diuretics could be ascertained.

Determinants of plasma potassium levels in diabetic ketoacidosis.

The classic proposal of intracellular K+ for extracellular H+ exchange as responsible for the hyperkalemia of diabetic ketoacidosis (DKA) has been questioned because experimentally induced organic anion acidosis fails to produce hyperkalemia. It has been suggested, instead, that the elevated serum [K+] of DKA might be the result of the compromised renal function, secondary to volume depletion, that usually accompanies DKA. However, several metabolic derangements other than volume depletion and acidosis, which are known to alter potassium metabolism, also develop in DKA. This study of 142 admissions for DKA examines the possible role of alterations in plasma pH, bicarbonate, glucose (G), osmolality, blood urea nitrogen (BUN) and plasma anion gap (AG) on the levels of [K+]p on admission. Significant (p less than 0.01) correlations of [K+]p with each of these parameters were found that could individually account for 8 to 15 percent of the observed variance in the plasma potassium levels; however, the effects of some or all of these parameters on the [K+]p could be independent and therefore physiologically additive. Since the parameters under study are themselves interrelated, having statistically significant correlations with each other, their possible independent role on [K+]p was evaluated by multiple regression analysis. Only plasma pH, glucose and AG emerged as having a definite independent effect on [K+]p, with no independent role found for bicarbonate, BUN and osmolality. The equation that best describes [K+]p on admission for DKA was: [K+]p = 25.4 - 3.02 pH + 0.001 G + 0.028 AG, (r = 0.515). These results indicate that the endogenous ketoacidemia and hyperglycemia observed in DKA, which result primarily from insulin deficit, are the main determinants of increased [K+]p. Since exogenous ketoacidemia and hyperglycemia in the otherwise normal experimental animal do not increase [K+]p, it is postulated that insulin deficit itself may be the major initiating cause of the hyperkalemia that develops in DKA. Renal dysfunction by enhancing hyperglycemia and reducing potassium excretion also contributes to hyperkalemia.

The Renal Diluting and Concentrating Mechanism in Hypercalcemia

The effects of acute hypercalcemia produced by infusing calcium lactate were studied in dogs during hydration and hydropenia. This allowed a direct observation of the effect of calcium on renal concen

Lessons from the hemodialysis (HEMO) Study: An improved measure of the actual hemodialysis dose

The Hemodialysis (HEMO) Study is a multicenter, prospective, randomized, 2 x 2 factorial clinical trial designed to evaluate the efficacy of the dose of dialysis delivered (standard v high) and dialysis membrane flux (low v high) in reducing the morbidity and mortality of patients. The study is nearly half complete. Although both patients and investigators are blinded to the overall findings, which will not be available for another 3 years, important data have been generated from which a more accurate expression has been derived for the dose of dialysis received by each patient in the trial. This new expression of the effectiveness of dialysis, eKt/V, is a two-pool approximation derived from the traditional single-pool Kt/V (spKt/V) and time on dialysis. The dialysis prescription for the HEMO Study subjects is individualized to achieve the target dose for each patient and is closely monitored by measuring the more accurate and validated expression of eKt/N. Comparisons of the HEMO Study dose of dialysis with other studies have been confused by this unique expression (eKt/V) of the dialysis dose and adequacy adopted for the HEMO Study. The target eKt/V dose in the standard arm of the Study is 1.05 and in the high arm is 1.45 per dialysis thrice weekly. Based on data available from 426 subjects randomized to each arm, the target of 1.05 in the standard dose of the HEMO Study is equivalent to an spKt/V of 1.32, and that of the high dose, 1.67. Thus, volunteers in the standard arm of the Study are receiving a tightly controlled and closely monitored dose, which is above the current national mean spKt/V, and above that of the accepted minimum standard spKt/N of 1.2. When completed, the HEMO Study will show whether there are merits of a tightly controlled hemodialysis dose that is consistently delivered over a prolonged period and whether a high dose is beneficial and safe to prescribe.

Functional Characteristics of the Diluting Segment of the Dog Nephron and the Effect of Extracellular Volume Expansion on its Reabsorptive Capacity

The functional characteristics of the ascending limb of Henles loop were examined during hypotonic saline infusion by measuring solutefree water clearance (C(H2O)) at varying rates of solute delivery. The influence of expansion of extracellular volume was studied by comparing C(H2O) during hypotonic saline diuresis in normal dogs with dogs whose extracellular volume had been expanded acutely by saline infusions or chronically by the administration of deoxycorticosterone acetate and salt. In normal animals hypotonic saline infusions greatly increased urine flow (V) and C(H2O) without appreciably augmenting osmolar clearance (C(osm)). C(H2O) was, therefore, analyzed as a function of V, rather than C(osm), since V was the best estimate of delivery of filtrate to the diluting segment. C(H2O) increased as a linear function of V without any evidence of saturation.The validity of interpreting increases in C(H2O) and V as indications of increased sodium reabsorption and delivery was reinforced by tissue studies that disclosed a rise in papillary osmolality with rising urine flows. The observed increase in C(H2O) and V could not, therefore, be due to a decrease in back diffusion of solute-free water as a result of a diminished osmotic driving force, but probably represented increased formation consequent to augmented delivery as a result of decreased fractional reabsorption in the proximal tubule. In animals whose extracellular volume was acutely or chronically overexpanded before the infusion of hypotonic saline, sodium excretion was greater, and C(H2O) less, at any given V. Although the curve relating C(H2O) to V was flatter than in the control group, no tubular maximum was observed. The diminished C(H2O) in this group was interpreted to mean that massive expansion of extracellular volume inhibits sodium reabsorption in the ascending limb of Henles loop.

The dialysis outcomes quality initiative: History, impact, and prospects☆

Rigorously developed clinical practice guidelines have the potential to improve patient outcomes. It is toward that end that the National Kidney Foundation (NKF) launched in March 1995 the Dialysis Outcome Quality Initiative (DOQI), an ambitious effort to develop evidence-based clinical practice guidelines for the care of patients with end-stage renal disease (ESRD). Independent, interdisciplinary work groups conducted a structured review of the content and methodologic rigor of all the published literature pertinent to four selected topics: hemodialysis adequacy, peritoneal dialysis adequacy, vascular access, and anemia. Following expert, organizational, and public review, the guidelines were issued in September and October 1997. An implementation plan that called for widespread dissemination of the guidelines and facilitation of adoption of them has resulted in their broad acceptance and Integration into quality improvement efforts. Additional guidelines on nutrition have recently been completed, while others on bone disease, hypertension, and hyperlipidemia are in various stages of planning or development. A major determinant of poor outcome of maintenance dialysis patients is the debilitated state of many individuals with ESRD at the time that they commence dialysis therapy. The recognition of this problem has stimulated an interest in extending the guidelines to management of patients with less severe renal insufficiency, well before they need renal replacement therapy; and to the early detection of renal insufficiency by a proteinuria and albuminuria risk assessment, detection, and elimination (PARADE) program. What started as an initiative to improve the quality of care of dialysis patients has evolved into a considerably expanded effort to making lives better for all individuals with any level of renal insufficiency.

Side Effects of Hemodialysis

Long-term hemodialysis for the therapy of endstage kidney disease has dramatically altered the otherwise fatal outcome of progressive renal disease. Clinical experience and technologic advances have reduced many of the difficulties and hazards associated with the procedure. As a result, some 10 per cent of the 55,000 patients on maintenance hemodialysis in the United States are able to perform the procedure at home, and many others undergo dialysis in centers with only limited medical supervision. These creditable achievements notwithstanding, sporadic cases of technical failure and serious complications continue to occur. More distressing to patients, however, are some of the recurrent .xa0.xa0.

An Overview of the National Kidney Foundation-Dialysis Outcomes Quality Initiative Implementation

Rigorously developed clinical practice guidelines have the potential to improve outcomes and favorably alter practice patterns. Because of widespread community concerns over the quality of dialysis care, the National Kidney Foundation initiated a Dialysis Outcomes Quality Initiative (NKF-DOQI) in March 1995 in an effort to create evidence-based best-practice clinical guidelines. Independent interdisciplinary Work Groups reviewed the available body of scientific literature on four selected topics: hemodialysis adequacy, peritoneal dialysis adequacy, vascular access, and anemia. More than 11,000 publications were identified, of which 1,500 were considered relevant and were subjected to structured review. Draft guidelines, with supporting rationales of their evidentiary basis, were subjected to a three-stage public and organizational review process. The final guidelines were issued in the fall of 1997. Because the potential benefit of guidelines depends on their implementation, planning for the implementation of NKF-DOQI was begun simultaneously with its review process. A 3-year implementation plan, with specific priorities and estimated costs, was developed and set into action by the end of 1997. The main objectives of the rather diverse and multifaceted plan of action are translating the NKF-DOQI Guidelines into clinical practice, building on what has been accomplished, and continued evaluation and review of the Guidelines.

Carpal tunnel syndrome and chronic hemodialysis.

Carpal Tunnel Syndrome and Chronic Hemodialysis Dear Sir, Referring to the letter by Walts et al. [1] published in your journal, our work is at odds with theirs. In our clinic we have monitored 176 patients in a program of chronic hemodialysis for periods ranging from 3 to 144 months (x = 67.6). Eight patients (3 male and 5 female) manifested carpal tunnel syndrome (CTS); their ages ranged from 40 to 81 years (x = 61.1). The duration of dialysis treatment was 91.5 months (range 72–144). These results contrast with the 176 months (14.7 years) that the said authors [1] speak of. Our work coincides with previously reviewed literature [2–5]. In 5 of these cases the syndrome was bilateral and in 3 unilateral (a total of 13 occurrences). In each case it was the arm with a functioning arteriovenous fistula which was affected; given that this was the sole vascular access no further surgical intervention was required. We pursued 5 anatomopathological studies with Congo red and thioflavine T manifesting a total of 9 interventions (8 patients). In only 1 case did we find deposits of amyloid. None of the affected patients presented indices of systemic amyloidosis. In the development of CTS, the patients in a program of chronic hemodialysis showed a marked preference for the arm carrying the vascular access despite the fact that neither vascular alterations nor inflammatory changes were noted in the anatomopathological studies effected. We observed no statistically significant relation with any special type of nephropathy such as presented by our patients: hyperuricemic nephropathy (2 cases), glomeru-lonephritis (2 cases), nephroangiosclerosis (1 case, showing the only incidence of amyloid deposits), tubular aci-dosis (1 case) and undefined etiologies (2 cases). Nor was any relation observed with the dialytic procedure, hypervolemia, or the various biochemical parameters studied (urea, creatinine, phosphocalcic metabolism, PTH and hematocrit count). According to our experience, CTS is a complication of periodic hemodialysis that does not show an elevated incidence of amyloid deposits, and in general appears after the sixth year of substitutive treatment. References Walts, A.E.; Goodman, M.D.; Matorin, P.A.: Amyloid, carpal tunnel syndrome, and chronic hemodialysis. Am. J. Nephrol. 5: 225–226 (1985). Halter, S.K.; DeLisa, J.A.; Stolov, W.C; Scardapane, D.; Sher-rard, D.J.: Carpal tunnel syndrome in chronic renal dialysis patients. Archs phys. Med. Rehabil. 62: 197–201 (1981). Schwarz, A.; Keller, F.; Seyfert, S.; Poll, W.; Molzahn, M.; Dist-ler, A.: Carpal tunnel syndrome: a major complication in long-term hemodialysis patients. Clin. Nephrol. 22: 133–137 (1984). Kachel, H.G.; Altmeyer, P.; Baldamus, C.A.; Koch, K.M.: Deposition of an amyloid-like substance as a possible complication of regular dialysis treatment. Contr. Nephrol. vol. 36, pp. 127–132 (Karger, Basel 1983).