Diabetic nephropathy: urinary albumin or total protein?
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Adult↗
Biomedical subjects
J Lemann
Publications and source records attributed to J Lemann.
Idiopathic hypercalciuria.
Idiopathic hypercalciuria, defined as the urinary excretion of more than 300 mg. calcium per day in men or more than 250 mg. calcium per day in women, or more than 4 mg. calcium per kg. per day, is observed in about 50 per cent of the patients with calcium oxalate/apatite nephrolithiasis and is one of the risk factors for stone formation. These patients do not exhibit hypercalcemia, elevated serum parathyroid hormone concentrations or urinary cyclic adenosine monophosphate excretion nor clinical evidence of sarcoidosis, other granulomas or a malignancy. Hypophosphatemia may be present. Augmented rates of intestinal absorption of dietary calcium account for most of the increments in urinary calcium. Serum 1,25-dihydroxyvitamin D concentrations are in the upper normal range or elevated among many patients and are normal but not suppressed in the others. Activation of 1,25-dihydroxyvitamin D formation may be secondary to hypophosphatemia or other, as yet undefined, factors. Since, 1,25-dihydroxyvitamin D apparently can up-regulate its own receptor, small increments in its synthesis and blood levels could amplify the effect of the hormone to stimulate intestinal calcium absorption. Calcium balances are slightly but significantly negative and urinary hydroxyproline excretion may be increased so that a generalized disorder of calcium homeostasis also involving bone may be present. Additional studies are required to determine the genetic basis for the occurrence of idiopathic hypercalciuria in families, the cause of greater expression of idiopathic hypercalciuria in men and whether environmental factors (high dietary sodium chloride, protein and purified carbohydrate intakes) contribute to the expression of idiopathic hypercalciuria. Although thiazide diuretics, inorganic phosphate, magnesium hydroxide and potassium citrate have provided effective therapy, prospective studies are needed to determine optimum therapy and the optimum duration of treatment.
Calcitriol↗
Potassium bicarbonate, but not sodium bicarbonate, reduces urinary calcium excretion and improves calcium balance in healthy men.
Previous studies demonstrated that the administration of NaHCO3 or sodium citrate had either only a small effect to reduce urinary Ca excretion or no effect, but that potassium citrate significantly reduced urinary Ca excretion. In order to further evaluate and compare the effects of NaHCO3 and of KHCO3, we performed ten metabolic balances in healthy men during 18 control days, 12 days of NaHCO3, 60 mmol/day and 12 days of KHCO3, 60 mmol/day. Six subjects were fed a low Ca diet (5.2 +/- 0.7 SD mmol/day) and three of these were also given calcitriol (0.5 microgram 6-hourly). Four subjects ate a normal Ca diet (19.5 +/- 1.3 mmol/day). For all 10 subjects, KHCO3 administration reduced urinary Ca excretion from control by -0.9 +/- 0.7 mmol/day, P less than 0.001. Net intestinal Ca absorption did not change detectably so that Ca balances became less negative by a +0.9 +/- 0.9 mmol/day; P = 0.01. KHCO3 administration was also accompanied by more positive PO4 and Mg balances. NaHCO3 administration had no significant effect on urinary Ca excretion or Ca balance. NaHCO3 and KHCO3 administration were accompanied by equivalently more positive Na or K balances, respectively and equivalently more negative acid balances (HCO3 retention). Neither NaHCO3 or KHCO3 altered fasting serum HCO3 concentrations, blood pH, serum 1,25-(OH)2-D or PTH concentrations. We conclude that KHCO3 promotes more positive Ca balances by either enhancing renal Ca retention or skeletal Ca retention or both.
Adult↗
Oxalate is overestimated in alkaline urines collected during administration of bicarbonate with no specimen pH adjustment.
We compared measurements of daily urine oxalate excretion in urines collected at the prevailing urine pH with measurements of urine oxalate excretion in urines collected into 20 mL of 6 mol/L HCl. We studied eight healthy adults fed constant diets. Urines were collected during control conditions and, in each subject, during the administration of NaCl, KCl, NaHCO3, or KHCO3, 90 mmol/day. Daily urine oxalate excretion calculated for collections made in acid averaged 271 (SD 79) mumol/day and did not vary with any of the salt supplements. When urines were collected at ambient urine pH (average 5.94, SD 0.23) during control conditions, and during the administration of NaCl or KCl, urine oxalate excretion averaged 263 (SD 88) mumol/day, a value not different from that for collections in acid. However, when urine was collected with no pH adjustment during NaHCO3 or KHCO3 administration (average pH 6.90, SD 0.14), apparent urine oxalate excretion averaged 398 (SD 132) mumol/day, significantly (P less than 0.025) exceeding the mean observed when urines were collected in acid. Moreover, the percentage increase in apparent oxalate excretion increased with urinary pH. These observations reinforce recommendations that urine specimens for measurement of oxalate be collected in acid to avoid the increase in apparent oxalate content that occurs during collection of alkaline urines. This increase presumably results from the well-known in vitro nonenzymatic conversion of ascorbate to oxalate.
Adult↗
Establishing the diagnosis of benign familial hematuria. The importance of examining the urine sediment of family members.
Patients with microscopic hematuria are generally referred for urologic investigation. We describe 30 patients with normal renal function referred to our clinic during the years 1970 through 1987 for evaluation of hematuria, usually microscopic, in whom prior urologic and radiological studies had failed to determine the cause of bleeding. Urinary sediment from the patients and first-degree relatives revealed hemoglobin and red blood cell casts; the inheritance pattern was consistent with autosomal dominant transmission. During follow-up for up to 18 years, renal function remained normal, thus confirming the diagnosis of benign familial hematuria. Immunoglobulin A nephropathy and Alport's syndrome were less common than benign familial hematuria and could be differentiated from it by history, physical examination, and routine laboratory testing. Since benign familial hematuria is a common disorder in adults with hematuria and normal renal function, urinary sediment from patients and family members should be examined before extensive urologic and radiological procedures are performed.
Adolescent↗
Cyclosporine therapy and refractory Pneumocystis carinii pneumonia. A potential association.
In surveillance of 75 patients receiving renal transplants in 1984 at our institution, five cases of Pneumocystis carinii pneumonia were detected. All five cases occurred in a subgroup of 11 patients who had received cyclosporine. A retrospective epidemiologic survey of the infected patients revealed all five were heterosexual white men with onset of Pneumocystis pneumonia two to six months after cadaveric transplantation. All received cyclosporine and corticosteroids, and four of five patients also received azathioprine; none was neutropenic or had evidence of concurrent cytomegalovirus infection. Only one of these patients responded to therapy with sulfamethoxazole and trimethoprim, one patient responded to pentamidine therapy, and the remaining three patients died. Cyclosporine use may be related to development of Pneumocystis infections that are refractory to conventional antiprotozoal therapy, and transplantation programs should closely survey patients for such complications.
Adult↗
Moderate hypocalcemia due to normal serum 1,25-dihydroxyvitamin D levels in an asymptomatic kindred with familial hypoparathyroidism.
Hypoparathyroidism was diagnosed in nine members of a kindred of three generations. This study investigated why these persons were asymptomatic and without developmental abnormalities, in contrast to the common presentation of idiopathic hypoparathyroidism. In the hypocalcemic subjects, serum calcium level was 7.4 +/- 0.8 mg/dl (mean +/- SD) and ionized serum calcium level was 3.48 +/- 0.21 mg/dl. Immunoreactive parathyroid hormone values were inappropriately low. Injection of EDTA in one patient lowered ionized calcium levels, but immunoreactive parathyroid hormone values did not rise. Serum levels of 1,25-dihydroxyvitamin D and other vitamin D metabolites were normal or elevated and substantially higher than in other hypoparathyroid states. The normally observed positive correlation between the fasting urinary calcium/creatinine ratio and serum 1,25-dihydroxyvitamin D that reflects the dependence of net bone resorption on 1,25-dihydroxyvitamin D was upheld in hypoparathyroid patients. It is proposed that the subjects with familial hypoparathyroidism in this kindred had moderate asymptomatic hypocalcemia without developmental abnormalities because normal or elevated serum 1,25-dihydroxyvitamin D levels enhanced intestinal calcium absorption. This may represent one point in the spectrum of idiopathic hypoparathyroidism. Alternately, both the moderate degree of hypocalcemia and the normal serum calcitriol values could have been related to mild, partial hypoparathyroidism, which could have been inherited in this kindred.
Calcium↗
Proteinuria in health and disease assessed by measuring the urinary protein/creatinine ratio.
We measured daily excretion rates for urinary protein and the ratios of urinary protein to creatinine in 24-h urines and in untimed urines in 60 healthy adults, 30 patients with kidney disease, and 22 kidney-transplant recipients. The ratios for urinary protein/creatinine, mg/g, in untimed urines and in 24-h urines from the same subjects were closely correlated (r = 0.97) for rates of protein excretion ranging from normal (mean 44 mg/day) to nephrotic (maximum 19,300 mg/day). Because urinary protein/creatinine in healthy subjects never exceeded 100 mg/g, we propose that a ratio of less than 100 mg/g in untimed urines, obtained in the absence of exercise, fever, or other evidence of urinary tract disease, is a criterion of normal kidney function. Among patients with nephrotic syndrome (urinary protein excretion rate greater than or equal to 4000 mg/day), urinary protein/creatinine ratios always exceeded 2000 mg/g in both 24-h and untimed urines. Intermediate urinary protein/creatinine ratios (100 to 2000 mg/g) may reflect any type of kidney disease.
Creatinine↗
The effect of parathyroidectomy on the recurrence of nephrolithiasis.
Little information is available on the long-term influence of parathyroidectomy on the rate of renal stone formation in patients with primary hyperparathyroidism (pHPT) and nephrolithiasis. The reported occurrence of renal stone disease in untreated patients with pHPT is 15% to 30%. A registry of 258 pHPT patients who underwent parathyroidectomies at the Milwaukee Regional Medical Center has allowed continued follow-up of the 71 (28%) pHPT patients with associated renal stone disease. Patients have been followed up for an average of 5 years (range, 1 to 15 years) since surgery. The rate of renal stone formation before and after parathyroidectomy was compared. Identification of a "new" renal stone was defined as passage and collection, extraction, or radiographic visualization of stones. All 71 pHPT patients with stone disease had hypercalcemia and inappropriately elevated parathyroid hormone concentrations, and after parathyroidectomy these values returned to normal in 69 of 71 patients. Since undergoing parathyroidectomy, only 4 patients have passed renal stones. The rate of stone formation per patient per year was 0.36 before and 0.02 after surgery (p less than 0.001). Surgical correction of pHPT significantly reduced the rate of stone formation.
Adult↗
The importance of renal net acid excretion as a determinant of fasting urinary calcium excretion.
To evaluate the effects of changing rates of fixed acid production on fasting urine Ca/creatinine, we studied five healthy men fed constant diets during control conditions (serum HCO3 27.3 +/- 2.6 SD mEq/liter and blood H+ 40.4 +/- 1.5 microEq/liter) and then during the administration of NH4Cl 3.0 mEq/kg/day (serum HCO3 22.5 +/- 4.9 mEq/liter; P less than 0.025, and H+ 46.8 +/- 2.3 mEq/liter; P less than 0.005). In addition to the expected increase in daily urinary Ca excretion from 5.2 +/- 2.0 to 12.5 +/- 3.0 mmole/day; P less than 0.001 as daily urinary net acid excretion was increased from 48 +/- 32 to 257 +/- 33 mEq/day; P less than 0.001 we observed that fasting urinary net acid/creatinine excretion also increased from 2.9 +/- 1.2 to 11.1 +/- 1.2 mEq/mmole creatinine; P less than 0.001 and fasting urine Ca/creatinine increased from 0.158 +/- 0.111 to 0.456 +/- 0.109 mmole/mmole creatinine; P less than 0.005. The additional Ca appearing in the urine during acidosis ultimately reflected augmented net bone resorption since daily urinary hydroxyproline excretion was increased from 0.232 +/- 0.062 to 0.377 +/- 0.108 mmole/day; P less than 0.01. Since variations in diet composition can cause fixed acid production and thus renal net acid excretion to vary from about zero to 200 mEq/day, such a range could cause fasting Ca/creatinine to vary from 0.09 to 0.37 mmole/mmole (0.03 to 0.13 mg/mg) and should be taken into account in the evaluation of fasting Ca/creatinine.
Acid-Base Equilibrium↗
Hydrochlorothiazide inhibits bone resorption in men despite experimentally elevated serum 1,25-dihydroxyvitamin D concentrations.
We evaluated the effects of hydrochlorothiazide administration in relation to Ca balance, the PTH and vitamin D endocrine systems, acid-base balance, and bone. We studied six healthy men fed constant diets providing only 5.1 +/- 0.7 SD mmoles Ca/day. Three of the men were also given calcitriol, 0.5 microgram 6-hrly throughout their studies. All subjects were observed during 18 control days and then during 18 days of hydrochlorothiazide (HTZ) administration, 25 mg 12-hrly. Observations during control days 11 through 16 were compared to those during days 7 through 18 of HTZ administration, inclusively. Directional changes during HTZ did not differ among subjects not given or given calcitriol. For all six subjects, control net intestinal Ca absorption, serum 1,25-(OH)2-D concentrations, serum iPTH concentrations, and daily urine cAMP excretion averaged 0.5 +/- 2.2 mmoles/day, 162 +/- 51 pM, 4.3 +/- 2.2 microliter Eq/ml and 4.2 +/- 0.9 mumoles/day, respectively; none changed during HTZ. As expected, HTZ administration was accompanied by a fall in urinary Ca excretion, averaging -1.4 +/- 0.8 mmoles/day; P less than 0.01. HTZ administration was also accompanied by less negative Ca balances, averaging +1.6 +/- 1.0 mmoles/day; P less than 0.025, and by a fall in daily urinary hydroxyproline excretion averaging -0.13 +/- 0.09 mmoles/day; P less than 0.025. We interpret these data to indicate that HTZ administration is accompanied by an inhibition of bone resorption. HTZ administration also raised serum HCO3 concentrations by +2.7 +/- 0.5 mEq/liter; P less than 0.001 and blood pH by + 0.05 +/- 0.02 units; P less than 0.005.(ABSTRACT TRUNCATED AT 250 WORDS)
Acid-Base Equilibrium↗
Calcitriol, calcium, and granulomatous disease.
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Calcitriol↗
Effects of weight loss on serum 1,25-(OH)2-vitamin D concentrations in adults: a preliminary report.
During a review of 42 metabolic studies in healthy women and men we observed that serum 1,25-(OH)2-D concentrations were directly correlated to the observed daily changes in body weight (r = 0.68; P less than 0.001) and to caloric intake/kg/day (r = 0.39; P = 0.01). These relationships could not be accounted for by related and physiologically expected changes in serum Ca or iPTH concentrations. However, serum 1,25-(OH)2-D concentrations were observed to be inversely correlated to serum PO4 levels (r = -0.44; P = 0.004). In addition, serum PO4 levels were inversely correlated to the daily changes in body weight (r = -0.40; P = 0.009). Since dietary sodium intake averaged 142 mmol/day, it is unlikely that the observed changes in weight were the result of changes in salt and water balance. Thus it seems reasonable to speculate that serum 1,25-(OH)2-D concentrations may vary directly with energy balance, as reflected by changes in body weight. This effect may be mediated by alterations in PO4 metabolism. The accurate assessment of serum 1,25-(OH)2-D levels thus appears to require several measurements over time periods during which body weight is stable.
Adult↗
Renal transplantation in primary oxaluria.
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Humans↗
Dietary calcium and serum 1,25-(OH)2-vitamin D concentrations as determinants of calcium balance in healthy men.
We previously reported that experimental elevations of serum 1,25-(OH)2-vitamin D [1,25-(OH)2-D] concentrations produced by the chronic oral administration of calcitriol, 0.75 micrograms every 6 hr, to healthy human males eating diets providing only 4 mmoles Ca/day stimulate net bone resorption as evidenced by more negative Ca balances and higher rates of urinary hydroxyproline excretion. To determine whether increased dietary Ca intake modifies this response we have compared serum 1,25-(OH)2-D and iPTH concentrations, Ca and PO4 balances, and urinary hydroxyproline excretion in three healthy human males adapted to diets providing 22.3 +/- 1.3 mmoles Ca/day and three healthy human males adapted to diets providing 9.3 +/- 0.7 mmoles Ca/day before and during the continuous oral administration of calcitriol 0.5 micrograms every 6 hr. For all six subjects, serum 1,25-(OH)2-D levels averaged 89 +/- 25 pM during control and 143 +/- 26 pM during calcitriol. Net intestinal Ca absorption and urinary Ca excretion rose during calcitriol but Ca balances did not change, averaging +2.2 +/- 2.2 mmoles/day during control and +4.3 +/- 2.2 mmoles/day during calcitriol for the subjects fed 22 mmoles Ca/day and -1.6 +/- 1.5 mmoles Ca/day during control and -1.7 +/- 2.0 mmoles Ca/day during calcitriol for the subjects fed 9 mmoles Ca/day. Urinary hydroxyproline excretion also did not change. Thus, when serum 1,25-(OH)2-D levels are elevated, the availability of dietary Ca appears to prevent more negative Ca balances and increased urinary hydroxyproline excretion suggesting that net bone resorption is not stimulated.
Adult↗
Phosphate deprivation increases serum 1,25-(OH)2-vitamin D concentrations in healthy men.
To re-evaluate whether phosphate-deprivation alters serum 1,25-(OH)2-D concentrations in men, we measured serum 1,25-(OH)2-D levels in seven healthy men while they ate constant diets providing 52.2 +/- 4.3 sd mmoles PO4/day for 12 days and then while they ate a diet providing 29.4 +/- 6.0 mmoles PO4/day and also were given Al(OH)3 for 18 days. Serum PO4 levels fell only transiently. Net intestinal PO4 absorption became indistinguishable from zero but, because of renal PO4 conservation, PO4 balances did not change. Nevertheless, serum 1,25-(OH)2-D concentrations increased from 80 +/- 21 pM during control to 104 +/- 26 pM; during PO4 deprivation; P less than 0.01. Net intestinal calcium (Ca) absorption tended to rise during PO4 deprivation, the individual increments being correlated to the increments in serum 1,25-(OH)2-D concentrations (r = 0.78; P less than 0.05). Urinary Ca excretion rose; P less than 0.001, the increments exceeding the increments in net intestinal Ca absorption so that Ca balances became more negative; P less than 0.001. Urinary hydroxyproline excretion did not change. Thus, as in women and animals, PO4 deprivation appears to cause enhanced net bone resorption apparently by reducing bone formation.
Adult↗
Bone resorption stimulated by elevated serum 1,25-(OH)2-vitamin D concentrations in healthy men.
We evaluated whether calcitriol administration to healthy men stimulates bone resorption. We compared serum 1,25-(OH)2-D concentrations, Ca and PO4 balances, and urinary hydroxyproline excretion rates in four healthy men adapted to a low Ca diet providing only 4.0 +/- 0.2 SD mmoles Ca/day to those in four healthy men eating a comparable diet (4.2 +/- 0.9 mmoles Ca/day) during the chronic oral administration of calcitriol, 0.75 micrograms every 6 hr. Serum 1,25-(OH)2-D levels averaged 94 +/- 16 pM during the control studies and 209 +/- 35 pM during calcitriol administration. Net intestinal Ca absorption averaged 0.5 +/- 0.3 mmoles/day during control and 1.8 +/- 0.5 mmoles/day during calcitriol (P less than 0.005), but urinary Ca excretion averaged 8.7 +/- 2.0 mmoles/day during calcitriol as compared to 2.9 +/- 1.4 mmoles/day during control (P less than 0.005). Thus, mean Ca balance, which averaged -2.4 +/- 1.2 mmoles/day during control, was more negative during calcitriol at -6.3 +/- 2.4 mmoles/day (P less than 0.05). Average daily PO4 balances averaged +7.7 +/- 1.5 mmoles/day during control but only tended to be negative during calcitriol at -1.1 +/- 5.4 mmoles/day, (NS). Urinary hydroxyproline excretion averaged 0.26 +/- 0.03 mmoles/day during control and 0.49 +/- 0.06 during calcitriol (P less than 0.001). We conclude that elevated serum 1,25-(OH)2-D concentrations in healthy men eating low Ca diets stimulate bone resorption.
Bone Resorption↗
Kidney transplant recipient with disseminated Strongyloides.
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Adult↗