Suitability of Estimated Glomerular Filtration Rate for Live Kidney Donor Selection.

INTRODUCTION: The assessment of the glomerular filtration rate (GFR) in kidney donor candidates is required for determining donor candidate acceptability. This assessment can be done using an estimated GFR (eGFR) or a measured GFR (mGFR). The primary objective of the present study was to compare, in healthy adult kidney donor candidates, GFR measured by the clearance of iothalamate to GFR estimated using the Chronic Kidney Disease Epidemiology Collaboration equation and to determine if eGFR was a suitable stand-alone assessment. A secondary objective was to explore demographic factors that affect the relationship of the eGFR and the mGFR. METHODS: A retrospective review of kidney donor candidates' records at the J. C. Walter, Jr., Transplant Center, Houston Methodist Hospital, from January 2013 to March 2016 was undertaken. GFR was measured by the plasma clearance of radioisotopic iothalamate and estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: The median mGFR was 108 mL/min/1.73 m2. The eGFR underestimated the mGFR by 11.5%. The underestimation was greatest in subjects with an mGFR of ≥90 mL/min/1.73 m2. The eGFR overestimated the mGFR in donor candidates of black race. CONCLUSIONS: The Chronic Kidney Disease Epidemiology Collaboration eGFR can be used for screening potential kidney donors restricting the use of iothalamate (mGFR) to those donors with an eGFR below the transplant centers' acceptable GFR threshold for donation, thereby effecting cost savings and greater donor convenience. The eGFR in black donor candidates should be used with caution.

Modulation of phosphate absorption by calcium in the rabbit proximal convoluted tubule.

Proximal convoluted (S2) and straight (S3) renal tubule segments were studied to determine the effect of Ca on lumen-to-bath phosphate flux (JlbPO4). Increasing bath and perfusate Ca from 1.8 to 3.6 mM enhanced JlbPO4 from 3.3 +/- 0.7 to 6.6 +/- 0.6 pmol/mm per min in S2 segments (P less than 0.001) but had no effect in S3 segments. Decreasing bath and perfusate Ca from 1.8 to 0.2 mM reduced JlbPO4 from 3.7 +/- 0.6 to 2.2 +/- 0.6 in S2 segments. These effects were unrelated to changes in fluid absorption and transepithelial potential difference. Increasing cytosolic Ca with a Ca ionophore, inhibiting the Ca-calmodulin complex with trifluoperazine, or applying the Ca channel blocker nifedipine had no effect on JlBPO4 in S2 segments. Increasing only bath Ca from 1.8 to 3.6 mM did not significantly affect JlbPO4. However, increasing only perfusate Ca enhanced JlbPO4 from 3.4 +/- 0.7 to 6.1 +/- 0.7 pmol/mm per min (P less than 0.005). Inhibition of hydrogen ion secretion, by using a low bicarbonate, low pH perfusate, both depressed base-line JlbPO4 and abolished the stimulatory effect of raising perfusate Ca. Net phosphate efflux (JnetPO4) also increased after ambient calcium levels were raised, ruling out a significant increase in PO4 backflux. When net sodium transport was abolished by reducing the bath temperature to 24 degrees C, JnetPO4 at normal ambient calcium was reduced and increasing ambient calcium failed to increase it, ruling out a simple physicochemical reaction wherein phosphate precipitates out of solution with calcium. The present studies provide direct evidence for a stimulatory effect of Ca on sodium-dependent PO4 absorption in the proximal convoluted tubule, exerted at the luminal membrane. It is postulated that Ca modulates the affinity of the PO4 transporter for the anion.

Functional characterization of the alpha adrenergic receptor modulating the hydroosmotic effect of vasopressin on the rabbit cortical collecting tubule.

To characterize the type of alpha adrenergic receptor, the effects of specific alpha adrenergic agonists and antagonists on antidiuretic hormone [( Arg8]-vasopressin [AVP])-induced water absorption were evaluated in cortical collecting tubules isolated from the rabbit kidney and perfused in vitro. In the presence of AVP (100 microU/ml), net fluid volume absorption (Jv, nanoliters per minute per millimeter) was 1.39 +/- 0.09 and osmotic water permeability coefficient (Pf, X 10(-4) centimeters per second) was 150.2 +/- 15.0. The addition of 10(-6) M phenylephrine (PE), an alpha adrenergic agonist, resulted in a significant decrease in Jv and Pf to 0.72 +/- 0.11 (P less than 0.005) and 69.9 +/- 10.9 (P less than 0.005). The addition of 10(-4) M prazosin (PZ), an alpha adrenergic antagonist, did not cause any significant change in Jv and Pf, which were 0.71 +/- 0.09 (P = NS vs. AVP + PE) and 67.8 +/- 9.5 (P = NS vs. AVP + PE), respectively. In a separate group of tubules, in the presence of AVP (100 microU/ml) and PE (10(-6) M), Jv and Pf were 0.78 +/- 0.17 and 76.1 +/- 18.0, respectively. The addition of 10(-6) M yohimbine (Y), an alpha 2 adrenergic antagonist, resulted in a significant increase in Jv to 1.46 +/- 0.14 (P less than 0.01) and Pf to 157.5 +/- 22.3 (P less than 0.005). Y (10(-4) M) or PZ (10(-4) M) alone did not significantly affect Jv and Pf in the presence of AVP )100 microU/ml). The effect of the natural endogenous catecholamine norepinephrine (NE) on Jv and Pf in the presence of AVP and propranolol (PR) was next examined. Jv and Pf were 1.53 +/- 0.07 and 176.3 +/- 5.2, respectively, in the presence of AVP (100 microU/ml) and PR (10(-4) M). The addition of NE (10(-8) M) resulted in a significant decrease in Jv to 1.19 +/- 0.11 (P less than 0.05) and Pf to 127.0 +/- 11.3 (P less than 0.02). Increasing the concentration of NE to 10(-6) M resulted in a further decrease in Jv and Pf to 0.70 +/- 0.10 (P less than 0.01 vs. NE 10(-8) M) and 68.5 +/- 10.6 (P less than 0.01 vs. NE 10(-8) M), respectively. The inhibitory effect of NE on AVP-induced water absorption was blocked by Y, but not by PZ. The effect of the alpha 2 adrenergic agonist clonidine (CD) on Jv and Pf was also examined. In the presence of AVP (10 microU/ml) Jv and Pf were 1.65 +/- 0.04 and 175.1 +/- 13.1, respectively. The addition of CD (10(-6) M) resulted in a significant decrease in Jv to 1.08 +/- 0.12 (P < 0.01) and Pf to 108.1 +/- 15.4 (P < 0.01). Increasing the concentration of CD to 10(-4) M resulted in a further significant decrease in Jv and Pf to 0.57 +/- 0.13 (P < 0.02 vs. CD 10(-6) M) and 54.7 +/- 13.8 (P < 0.01 vs. CD 10(-6) M), respectively. Similar results were obtained in the presence of AVP (100 microU/ml). The inhibitory effect of CD on AVP-induced water absorption was blocked by Y. CD did not significantly affect Jv and Pf in the presence of 8-bromo adenosine 3',5'-cyclic monophosphate. These studies indicate that alpha adrenergic agonists directly inhibit AVP-mediated water absorption at the level of renal tubule, an effect that can be blocked by specific alpha2 adrenergic antagonists, but not by specific alpha1 adrenergic antagonists. Alpha2 adrenergic stimulation directly inhibits AVP-mediate water absorption at the level of the tubule, an effect that can be blocked by a specific alpha2 adrenergic antagonist. This effect appears to be exerted at the level of activation of adenylate cyclase, since it is absent in the present of cyclic AMP.

Calcium transport in the pars recta and thin descending limb of Henle of the rabbit, perfused in vitro.

Unidirectional calcium flux (JCa) in the superficial pars recta and thin descending limb of Henle (DLH) was examined by the isolated tubule microperfusion technic using 45Ca as the isotopic tracer. In the pars recta sequential measurements of lumen-to-bath flux (JlbCa) and bath-to-lumen flux (JblCa) revealed: JlbCa 22.4 +/- 4.18, JblCa 7.97 +/- 1.95, and calculated net efflux of calcium (JnetCa 13.0 +/- 1.74 peq min-1 mm-u. To measure JnetCa directly, 45Ca of identical specific activity was used to bathe and perfuse the tubule. These studies revealed: JlbCa 14.1 +/- 1.33, JnetCa 11.2 +/- 1.15, and calculated JblCa 2.91 +/- 0.49 peq min-1 mm-1. The addition of ouabain (10 microM) resulted in a rise in potential difference and a fall in water absorption, but not a statistically significant change in JnetCa. Tubules studies at 25 degrees C bath temperature, showed no significant JnetCa, and upon heating the bath to 37 degrees C, showed JnetCa of 3.75--5.00 peg min-1 mm-1. Unidirectional and net efflux studies in six DLH showed no significant transport of calcium. These studies demonstrate substantial active absorption of calcium by the superficial pars recta, which is not inhibitable by ouabain but is inhibited by lowering bath temperature to 25 degrees C. No significant calcium transport was found in the DLH using identical technics.

The influence of the extracellular fluid volume on the tubular reabsorption of uric acid.

Changes is tubular reabsorption of uric acid in response to alterations in the extracellular fluid volume (ECFV) were examined in rats by clearance studies and by direct intratubular microinjections. Contraction of the ECFV led to a rise in the serum uric acid concentration and a 47% decrease in the clearance of uric acid. The ratio of uric acid to inulin clearance also fell, indicating an increase in the net tubular reabsorption of urate. Volume expansion resulted in an increase in the urate clearance and a 37% decrease in the net tubular reabsorption of uric acid. To localize the site in the nephron where these changes occur, microinjections of [2-14C]urate were performed. The lack of conversion of radioactive urate to allantoin after microinjections was demonstrated by thin-layer chromatography. After contraction of the ECFV, urinary recoveries of uric acid were significantly decreased after microinjections into proximal tubular sites. In contrast, recoveries were increased from these proximal sites after volume expansion. No evidence for distral reabsorption was obtained in any group of animals. These studies demonstrate that net urate reabsorption is influenced by the state of hydration of the ECFV and that these alterations are mediated by changes in the rates of reabsorption in the proximal tubule.

Calcium transport in the rabbit superficial proximal convoluted tubule.

Calcium transport was studied in isolated S2 segments of rabbit superficial proximal convoluted tubules. 45Ca was added to the perfusate for measurement of lumen-to-bath flux (JlbCa), to the bath for bath-to-lumen flux (JblCa), and to both perfusate and bath for net flux (JnetCa). In these studies, the perfusate consisted of an equilibrium solution that was designed to minimize water flux or electrochemical potential differences (PD). Under these conditions, JlbCa (9.1 +/- 1.0 peq/mm X min) was not different from JblCa (7.3 +/- 1.3 peq/mm X min), and JnetCa was not different from zero, which suggests that calcium transport in the superficial proximal convoluted tubule is due primarily to passive transport. The efflux coefficient was 9.5 +/- 1.2 X 10(-5) cm/s, which was not significantly different from the influx coefficient, 7.0 +/- 1.3 X 10(-5) cm/s. When the PD was made positive or negative with use of different perfusates, net calcium absorption or secretion was demonstrated, respectively, which supports a major role for passive transport. These results indicate that in the superficial proximal convoluted tubule of the rabbit, passive driving forces are the major determinants of calcium transport.

Calcium transport in the thick ascending limb of Henle. Heterogeneity of function in the medullary and cortical segments.

Calcium transport was studied in medullary and cortical segments of the thick ascending limb of Henle perfused in vitro. 45Ca was added to the perfusate for measuring lumen-to-bath flux (JlbCa), to the bath for measuring bath-to-lumen flux (JblCa), or to both perfusate and bath for measuring net flux (JnetCa). In the medullary segment JlbCa exceeding JblCa and the efflux:influx coefficient ratio was not different from the value predicted from the observed potential difference (PD). In the cortical segments, however, efflux:influx coefficient ratio was greater than the value predicted from the PD, suggesting that calcium transport in this segment may be active, while it is passive in the medullary segment. Furosemide, which reversibly decreases PD in both cortical and medullary segments, inhibited JlbCa only in the medullary segment. Parathyroid hormone (PTH), on the other hand, had no effect on JnetCa in the medullary segment, but it significantly augmented JnetCa in the cortical segment. These results indicate that calcium transport in the thick ascending limb is heterogeneous. In the medullary segment it is passive, inhibited by furosemide and not influenced by PTH. In the cortical segment, however, calcium transport appears to be active, not inhibited by furosemide and stimulated by PTH.

Effect of expansion of extracellular fluid volume on renal phosphate handling.

To examine the specific effect of extracellular fluid (ECF) volume expansion on phosphate excretion studies were performed in thyroparathyroidectomized dogs receiving saline solution intravenously. The natriuresis resulting from ECF volume expansion was consistently accompanied by an increase in phosphate excretion. The possible role of increased filtered load of phosphate was eliminated in experiments in which the filtered load of phosphate was reduced by acute reduction in the glomerular filtration rate. Despite considerable reductions in filtered phosphate, ECF volume expansion resulted in a consistent increase in phosphate excretion. Furthermore, the possible contribution of alteration in blood composition was investigated in experiments in which saline was infused during thoracic inferior vena cava constriction. In these experiments saline infusion failed to increase sodium or phosphate excretion. Cessation of saline infusion and release of caval constriction resulted in a prompt natriuresis and increased phosphate excretion. It is concluded from these studies that extracellular fluid volume expansion results in an increased phosphate excretion in the parathyroidectomized dog. This effect is the specific consequence of ECF volume expansion and is not due to increase in the filtered load of phosphate or alterations in blood composition.

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 Henle's 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 Henle's loop.

Modulation of the hydro-osmotic effect of vasopressin on the rabbit cortical collecting tubule by adrenergic agents.

The effects of catecholamines on antidiuretic hormone ([Arg(8)]-vasopressin [AVP])-induced water absorption were evaluated in cortical collecting tubules isolated from the rabbit kidney and perfused in vitro. In the presence of AVP (100 muU/ml), net fluid volume absorption (J(v), nanoliters per minute per millimeter) was 1.14+/-0.12 and osmotic water permeability coefficient (P(f), X 10(-4) centimeters per second) was 217.3+/-39.9. The addition of the alpha-adrenergic agonist, phenylephrine (PE), in a concentration of 10(-6) M resulted in a significant decrease in J(v) and P(f) to 0.83+/-0.13 (P < 0.001) and 148.8+/-41.8 (P < 0.02), respectively. Increasing the concentration of PE to 10(-5) M resulted in a further decrease in J(v) and P(f) to 0.53+/-0.05 (P < 0.05 vs. PE 10(-6) M) and 88.5+/-9.0 (P 0.05 vs. PE 10(-6) M), respectively. In a separate group of tubules, in the presence of AVP (100 muU/ml) and PE (10(-5) M), J(v) and P(f) were 0.35+/-0.07 and 66.0+/-17.3, respectively. The addition of the alpha-adrenergic antagonist, phentolamine (PH), in a concentration of 10(-6) M resulted in a significant increase in J(v) to 1.07+/-0.19 (P < 0.001) and P(f) to 193.3+/-35.9 (P < 0.005). PH (10(-5) M) alone did not significantly affect J(v) and P(f) in the presence of AVP (100 muU/ml) nor in the presence of 8-bromo adenosine 3',5' cyclic monophosphate (8-BrcAMP). J(v) and P(f) were 1.20+/-0.21 and 174.0+/-25.8, respectively, in the presence of 8-BrcAMP (10(-4) M). We next examined the effect of the beta-adrenergic agonist, isoproterenol (ISO), on J(v) and P(f) in the presence of AVP. J(v) and P(f) were 1.04+/-0.10 and 202.6+/-17.2, respectively, in the presence of AVP (100 muU/ml) and 1.06+/-0.18 and 193.4+/-27.7, respectively, in the presence of AVP (10muU/ml). However, in the presence of AVP in a concentration of 2.5 muU/ml, J(v) was 0.60+/-0.07 and P(f) was 100.7+/-24.7. ISO (10(-6) and 10(-5) M) did not have any significant effect in the presence of the above maximal and submaximal concentrations of AVP. In the absence of AVP, control J(v) was 0.01+/-0.12 and P(f) was 4.6+/-11.0. The addition of ISO at 25 or 37 degrees C did not result in any significant change in J(v) or P(f). These studies indicate that alpha-adrenergic agonists directly inhibit AVP-mediated water absorption at the level of the tubule, an effect that can be blocked by a specific alpha-adrenergic antagonist. This effect appears to be exerted at the level of activation of adenylate cyclase since it is absent in the presence of cAMP. The beta-adrenergic agonists do not directly inhibit or enhance AVP-mediated water absorption at the level of the renal tubule.

Effects of volume expansion, purified parathyroid extract, and calcium on renal bicarbonate absorption in the dog.

The role of parathyroid hormone (PTH) and of Ca(++) in the regulation of bicarbonate absorption (RHCO(3)) and its response to extracellular volume expansion (VE) was studied in HCO(3) (-)-loaded dogs.VE lowered RHCO(3) in both intact (from 24.8 to 22.0 mmol/liter GFR, P < 0.01) and thyroparathyroid-ectomized (TPTX) (from 24.5 to 18.0 mmol/liter GFR, P < 0.001) dogs; glomerular filtration rate (GFR) and filtered HCO(3) (-) did not change. Both groups showed a significant increase in the fractional excretion of sodium (C(Na) x 100/GFR), calcium (C(Ca) x 100/GFR), and chloride (C(Cl) x 100/GFR) and a decrease in phosphorus reabsorption. Fractional clearance of phosphate (C(P) x 100/GFR) rose in both groups but did not achieve significance. Infusion of purified parathyroid extract (PTE) decreased RHCO(3) in intact dogs (from 24.6 to 22.5 mmol/liter GFR, P < 0.025) and in TPTX dogs (from 26.9 to 22.6 mmol/liter GFR, P < 0.05). No change was noted in GFR, renal blood flow (RBF), filtered HCO(3) (-), or fractional excretion of sodium, calcium, or chloride in either group. There was a significant increase in fractional phosphorus clearance and a decrease in phosphorus reabsorption in each group. Infusion of Ca(++) raised ultrafilterable Ca(++) from 5.7 to 7.9 mg/100 ml in intact and from 4.9 to 7.2 mg/100 ml in TPTX dogs; RHCO(3) increased in intact (from 22.9 to 26.9 mmol/liter GFR, P < 0.025) and in TPTX dogs (from 26.6 to 28.6 mmol/liter GFR, P < 0.05). The GFR, RBF, and the fractional excretion of sodium, chloride, and calcium did not change in either group. The reabsorbed phosphate increased in both groups, and fractional phosphorus clearance fell in the intact group but did not change significantly in the TPTX group. Superimposition of PTE on hypercalcemia in TPTX dogs resulted in a decrease in RHCO(3) (from 27.3 to 23.9 mmol/liter GFR, P < 0.001), which was accompanied by an increase in the fractional excretion of phosphate and a decrease in the reabsorbed phosphate. In this group of TPTX dogs hypercalcemia caused a drop in RBF from 135.6 to 105.8 ml/min with no change in GFR. The RBF returned to control value with PTE infusion. IT IS CONCLUDED THAT: (a) the lowering of RHCO(3) by VE is not dependent solely on stimulation of PTH by the lowered Ca(++), (b) PTE acts directly on the renal tubules to lower RHCO(3), (c) Ca(++) enhances RHCO(3) and this effect is exerted in the absence of PTH and calcitonin, (d) neither the effects of Ca(++) nor of PTH appear to be mediated by altered hemodynamics, although this cannot be excluded in Ca(++)-infused TPTX dogs, (e) Ca(++) enhanced phosphate reabsorption in the absence of PTH; this may be a specific effect of hypercalcemia on phosphate reabsorption or the nonspecific consequence of the rise in serum phosphorus.

Effects of glucose on bicarbonate reabsorption in the dog kidney.

The effects of glucose on renal bicarbonate reabsorption were investigated in the dog. The infusion of small amounts of glucose calculated to slightly exceed the renal threshold for glucose absorption increased bicarbonate reabsorption in bicarbonate loaded dogs. Galactose in similar doses also increased the reabsorption of filtered bicarbonate. This effect is not due to insulin secretion since insulin alone did not alter bicarbonate reabsorption and the infusion of glucose into alloxan-diabetic dogs given a steady infusion of insulin also enhanced bicarbonate reabsorption. It is more likely that the increased tubular reabsorption of glucose, secondary to an increased filtered load, resulted in the increase in bicarbonate reabsorption since phlorizin reversibly inhibits the effect of glucose.

Blastogenic suppression and alloantibody activity of sera from renal allograft recipients.

To evaluate whether immunological enhancement plays a role in adaptation to renal allografts, we studied sera from transplant recipients to determine whether those which suppressed mixed leukocyte culture (MLC) responses in vitro contained alloantibodies reactive with donor cells. Sera from five of nine renal transplant recipients consistently and specifically suppressed autologous autologous MLC responses to donor cells without impairing the blastogenic responses to third-party leukocytes, soluble antigens, or nonspecific mitogenic agents. In three of the five cases the suppressive activity of the serum was striking; in two cases the effect was less marked but still readily demonstrable in studies designed to evaluate the dose of serum which provided optimal suppression of MLC responses. Serum from one of the recipients nonspecifically suppressed blastogenic activity both to donor cells and other stimuli. No alloantibody reactive with donor leukocytes was found in any of the sera which exhibited suppressive activity in MLC, whereas in one patient, serum which contained antibody reactive with donor cells did not suppress MLC response to that donor. These findings suggest that, if the serum factors which suppress MLC responses in vitro are enhancing antibodies, they are not detectable even with very sensitive techniques either because they are present in very low concentrations, belong to immunoglobulin classes other than IgA, IgG, or IgM, or are complexed with donor antigen in such a way that their ability to react with fresh donor cells in vitro is blocked.

Renal hemodynamic consequences of angiotensin-converting enzyme inhibition in congestive heart failure.

Angiotensin-converting enzyme (ACE) inhibitors are of benefit in the management of heart failure. In some studies in patients with heart failure, a decline in renal function occurred more frequently in patients treated with enalapril maleate, a longer-acting agent, than in those treated with captopril, a shorter-acting drug. Patients experiencing a decline in renal function had a number of predisposing hormonal and hemodynamic factors. In one report, these factors included an initial fall in blood pressure that was sustained, lower cardiac output, and a relatively high fixed dose of enalapril that contributed to renal impairment. In a second study, the decline in renal function was most severe in patients with a lower systemic arterial pressure in whom glomerular filtration may have been dependent on angiotensin II. In a third study, intravascular volume depletion and an activated renin-angiotensin system led to reduced renal function. Reduction of angiotensin II level in plasma and tissues by ACE inhibitors decreases systemic vascular resistance and efferent arteriolar tone, which tends to decrease glomerular filtration rate. If compensatory increases in cardiac output are inadequate or preexisting renal impairment or volume depletion is present, renal function will deteriorate. Long-acting ACE inhibitors prolong the decreased efferent arteriolar tone and may compromise cardiac muscle response to catecholamines. The use of shorter-acting agents in patients who exhibit deterioration in renal function may be preferable.

Acute glomerulonephritis complicating diabetic nephropathy.

Diabetes mellitus is a systemic disorder that affects many organs in the body. Diabetic nephropathy occurs a number of years after the onset of the disease, and it is usually manifested by the development of the nephrotic syndrome. However, the sudden onset of massive proteinuria or the rapid deterioration of renal function in the stable diabetic patient should suggest that an additional pathologic condition is affecting the kidneys. We report three cases of diabetic nephropathy complicated by other superimposed renal diseases.

Indomethacin treatment of pericarditis in chronic hemodialysis patients.

Symptomatic pericarditis occurs in the course of maintenance hemodialysis and often requires pericardiectomy in addition to other conventional measures. Three of 11 such patients were treated with frequent dialysis and general supportive treatment. Two of these required pericardiocentesis. The other eight received indomethacin; this was followed by prompt defervescence and abatement of pain within 6 to 24 hours. Only one patient required pericardiocentesis. On every occasion when treatment was discontinued during the first week, symptoms recurred. After three weeks to four months, the drug dosage could be tapered and discontinued. The pericardial aspirate was hemorrhagic in all three patients who required pericardiocentesis. Indomethacin appears to be effective in the treatment of the pericarditis associated with dialysis and precludes the need for invasive procedures.

Plasma cells in urine: occurrence in multiple myeloma.

Numerous plasma cells were transiently found in the urine of a patient with multiple myeloma. The patient was in acute renal failure, and she had K-type Bence-Jones proteinemia and proteinuria. A slide of stained urine sediment showed cells with freatures characteristic of plasma cells. Their cytoplasm was highly reactive with anti-K antiserum on immunofluorescence, suggesting that these were myeloma cells.

Calciphylaxis in man. A syndrome of tissue necrosis and vascular calcification in 11 patients with chronic renal failure.

Eleven patients with chronic renal failure and presumed secondary hyperparathyroidism developed a syndrome of medial calcinosis of the arteries and painful ischemic ulcers of the fingers, legs, or thighs, or any combination of the three. Five patients required maintenance hemodialysis; six had functioning renal homografts. Severe hyperphosphatemia had existed in each; seven showed roentgenographic evidence of subperiosteal resorption. Similarities are evident between the lesions and experimentally produced calciphylaxix. The lesions demonstrated a relentless, progressive course, with serious morbidity and mortality. Hyperplastic or adenomatours parathyroid tissue was removed from ten of 11 patients unergoing surgical procedures; healing followed in seven patients. Treatment with phosphate-binding antacids to lower serum phosphorus levels may prevent this syndrome. Total or subtotal parathyroidectomy should be considered when ischemic skin lesions appear in uremic patients or in renal transplant recipients.

The human genome encodes at least three non-allellic G proteins with alpha i-type subunits.

The amino acid sequence and composition of alpha-subunits of signal transducing G proteins of the same kind appear to vary by no more than 2% from species to species. Here we isolated a human liver cDNA using an oligonucleotide complementary to the sequences encoding the pertussis toxin (PTX) ADP-ribosylation site of the alpha-subunit of the rat brain G protein called Gi. Its open reading frame characterizes it as an alpha i-type cDNA--as opposed to alpha o-type--but predicts an amino acid composition that differs by 7% and 14%, respectively, from two other human alpha i-type molecules. Together with human brain alpha i (type-1) and human monocyte alpha i (type-2), the new human liver alpha i cDNA (type-3) forms parts of a family of alpha i molecules. Type-3 alpha i cDNA hybridizes to a approximately 3.6 kilobase long mRNA and type-2 alpha i cDNA hybridizes to an mRNA species of approximately 2.7 kilobases. This indicates that the human genome has at least three non-allellic genes encoding non-alpha o-type PTX substrates and provides structural evidence for the hypothesis that distinct effector systems are regulated by similar but nevertheless distinct PTX substrates.

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.