Renal tubular dysfunction in patients with cystic disease of the kidneys.

OBJECTIVE: To define the renal tubular functional abnormalities in patients with cystic disease of the kidneys. METHODS: Patients with autosomal dominant polycystic kidney disease (ADPKD) (n = 4) and medullary sponge kidneys (MSK) (n = 3) with normal glomerular filtration rate (GFR), determined by inulin clearance, and effective renal plasma flow (ERPF), measured by p-aminohippurate clearance, underwent measurement of proximal and distal tubular functions. Proximal tubular functions were determined by the maximum reabsorption of glucose (TmGlucose) and the maximum secretion of p-aminohippurate (TmPAH). Distal tubular functions were measured by the maximum urinary concentrating and diluting mechanisms, and the urinary acidification response to acid load. RESULTS: TmGlucose was low in both groups (209 +/- 25 mg/min/1.73 m2 in the ADPKD group and 110 +/- 28 mg/min/1.73 m2 in the MSK, compared with 375 +/- 40 mg/min/1.73 m2 in healthy controls; P < 0.05). Likewise, TmPAH was significantly diminished in patients with ADPKD (72 +/- 6 mg/min/1.73 m2) and MSK (63 +/- 5 mg/min/1.73 m2) when compared with healthy controls (89 +/- 4 mg/min/1.73 m2; P < 0.05). Urinary maximum concentration after fluid deprivation was impaired in both ADPKD and MSK patients, but the diluting mechanism was intact. Finally, the ability to excrete urinary ammonium and titratable acids following an oral acid load was inadequate in both the ADPKD and MSK groups. CONCLUSIONS: Proximal and distal tubular functions are impaired in patients with ADPKD and MSK when GFR and ERPF are normal, indicating tubular disruption by the cysts and the alteration of the tubulo-interstitial vascular relationship.

Diagnosis of renal artery stenosis in transplanted kidneys: value of Doppler waveform analysis of the intrarenal arteries.

OBJECTIVE: The objective of this study was to determine in renal transplant patients if the acceleration time and subjective assessment of dampening of the waveforms from the intrarenal arteries improves the accuracy of detecting a hemodynamically significant (> or = 50%) proximal arterial stenosis compared with measurements of peak systolic velocity from a main renal artery. MATERIALS AND METHODS: In 15 patients, the findings of 19 Doppler sonograms and corresponding arteriograms of their renal transplants were reviewed, with arteriography serving as the gold standard. Four patients had a significant proximal arterial stenosis; three were of the main renal artery and one was of the adjacent external iliac artery proximal to the anastomosis with the renal artery. RESULTS: We found a significant prolongation of the acceleration time in patients with a significant proximal arterial stenosis (p = .0004). Use of a threshold acceleration time of 0.10 sec or subjective assessment of dampening of the waveforms resulted in an accuracy of 95% in detecting a significant proximal arterial stenosis. This compared with an accuracy of 62% in detecting a significant proximal arterial stenosis using a peak systolic velocity threshold of 2.0 m/sec as the sole criterion. Using intrarenal arterial Doppler waveform parameters alone would have spared arteriography in 11 patients and would have detected three of four significant proximal arterial stenoses. CONCLUSION: In this study, Doppler waveform analysis of the intrarenal arteries improved the accuracy of screening for a significant proximal arterial stenosis. The results suggest that such analyses can be used to spare many patients with suspected renal vascular hypertension from unnecessary arteriography.

Evaluation of the renal arteries in kidney donors: value of three-dimensional phase-contrast MR angiography with maximum-intensity-projection or surface rendering.

OBJECTIVE: Donors routinely undergo preoperative conventional arteriography to evaluate the renal arteries before nephrectomy. The purpose of this study was to assess the capability of three-dimensional phase-contrast MR angiograms postprocessed with maximum-intensity-projection and surface-rendering techniques to show the renal arteries of potential donors. MATERIALS AND METHODS: Postprocessed three-dimensional phase-contrast MR angiograms of 17 patients were retrospectively reviewed by two experienced radiologists for the number and length of renal arteries visualized. Conventional arteriograms were used as the reference standard. Coronal maximum-intensity-projection and surface-rendered MR angiograms were also compared with each other with regard to the delineation of renal arteries from overlapping vessels. RESULTS: MR angiograms showed all 34 single or dominant renal arteries but only eight of 10 accessory arteries seen on conventional arteriograms. One of the nonvisualized accessory arteries was located within the imaged volume, and the other one arose from the distal aorta beyond the imaged regions. Five of six arterial branches arising from the proximal 30-mm portions of the renal arteries were seen on MR angiograms. Postprocessing with either maximum-intensity projection or surface-rendering showed the same number of renal arteries, although surface rendering separated overlapping veins from the renal arteries better than the maximum-intensity-projection technique. CONCLUSION: These results suggest that three-dimensional MR angiography is a reliable method of imaging single or dominant renal arteries, but not for showing all accessory renal arteries and small arterial branches. Surface rendering may provide specific advantages over maximum-intensity-projection in delineating renal arteries from overlapping vessels.

Mechanism of glomerular hyperfiltration after a protein meal in humans. Role of hormones and amino acids.

OBJECTIVES: Previous studies demonstrated that protein meals and amino acid (AA) infusions increase glomerular filtration rate (GFR) and renal plasma flow (RPF) and that somatostatin (SRIH) infusion inhibits these increments. We tested whether a single AA such as alanine could increase GFR and RPF and whether the changes in GFR and RPF could be explained on the basis of changes in glucagon, growth hormone (GH), and insulin. RESEARCH DESIGN AND METHODS: In the first experiment, alanine was infused with or without SRIH in five normal subjects. In the second experiment, five other subjects were infused with SRIH on three separate occasions. In a control study, insulin, glucagon, and GH were given at replacement doses; in a hyperglucagonemia study, glucagon was given at a rate of 0.2 microgram.kg-1.h-1 (hypoglucagonemia); and in a high GH study, GH was given at a rate of 2 micrograms.kg-1.h-1. GFR and RPF were measured using insulin and para-aminohippurate, respectively. RESULTS: Alanine increased GFR and RPF, whereas SRIH inhibited these changes (P < 0.05). Hyperglucagonemia or high GH with or without insulin failed to increase RPF or GFR. CONCLUSIONS: A single AA such as alanine increases GFR and RPF, and this increase is dependent on a factor inhibited by SRIH. Although GH, glucagon, and insulin are factors inhibited by SRIH, none of these factors explains the changes in RPF and GFR in our acute studies.

Renal handling and physiologic effects of the paramagnetic contrast medium Gd-DOTA.

Gadolinium DOTA (Gd-DOTA) is a magnetic resonance (MR) contrast agent similar to Gd-DTPA but with greater stability in vitro. The effects of a high intravenous dose (0.5 mmol/kg) of Gd-DOTA (1360 mOsm/kg) on renal excretory function and its general systemic effects are examined in this animal study. This dose was selected to accentuate and better define the qualitative nature of these effects. A decrease in arterial pressure of 8% (131.9 +/- 6.8 at 120 minutes versus a control of 142.8 +/- 3.7 mm Hg, mean +/- standard error of mean, no significant change in electrocardiogram (ECG) lead II, a 16% increase in renal blood flow (106.0 +/- 5.4 at 7.5 minutes versus 91.2 +/- 3.2 ml/min), and a decrease in arterial hematocrit of 9% (38.9 +/- 1.5 at 120 minutes versus 41.9% +/- 1.7%) were noted. In general, qualitatively similar effects have been noted as a nonspecific effect of other hyperosmolar solutions. The filtration fraction decreased (0.23 +/- 0.01 at 7.5 minutes versus 0.28 +/- 0.02) followed by a rapid return to baseline values. No significant change was noted in glomerular filtration rate throughout the experimental protocol. Urine flow increased nearly 1.5-fold and osmolal clearance (Cosm) increased approximately 1.5 times. A natriuresis occurred as the fractional excretion of sodium (FENa+) increased from a control value of 3.5 +/- 0.3 to 5.2 +/- 0.5 at 7.5 minutes. The systemic and renal physiologic effects of high-dose intravenous Gd-DOTA on the kidney reflects a nonspecific, osmotically induced alteration. These data suggest that the main systemic and renal physiologic actions of Gd-DOTA are a nonspecific response to agent osmolality that is similar qualitatively to conventional, water-soluble contrast media.

Potassium homeostasis during angiotensin-converting enzyme inhibition with enalapril.

The effect of angiotensin-converting enzyme (ACE) inhibition on renal and extrarenal potassium (K) regulation was examined. Six healthy men were studied in double-blinded crossover fashion on placebo or enalapril, 80 mg/day. On day 4, the subjects were given an intravenous infusion of KCl and on day 5 an oral dose of 10% NH4Cl. Treatment with enalapril decreased plasma aldosterone and increased plasma renin activity (PRA), epinephrine and norepinephrine, but did not affect serum glucose, plasma insulin or basal plasma K. Maximal increases in plasma K during K infusion or NH4Cl ingestion were similar during enalapril and placebo treatment. With enalapril treatment urinary K excretion was unchanged following K loading but moderately reduced following NH4Cl loading. We conclude that ACE inhibition does not acutely impair K homeostasis in men with normal renal function.

Renal tubular dysfunctions in patients with idiopathic calcium nephrolithiasis.

To define the degree of renal tubular involvement in idiopathic calcium nephrolithiasis, 18 patients (aged 23-60 years, 15 men and 3 women, with 1-30 years of renal stone history) with normal glomerular filtration rate (GFR) and effective renal plasma flow with no history of urinary tract infection and on no dietary or drug therapy underwent the following studies: measurement of proximal tubular maximum reabsorption of glucose (Tmglucose) and secretion of para-aminohippurate (TmPAH), urinary concentrating ability after 14 h of fluid deprivation, and urinary net acid excretion following an oral dose of ammonium chloride, 0.1 g/kg of body weight. Seventeen healthy subjects in the same age range served as control. Patients with calcium nephrolithiasis, with normal renal hemodynamic functions, have significantly lower proximal tubular maximum reabsorptive and secretory functions, diminished urinary concentrating mechanism, and reduced urinary net acid excretion following an oral acid load. These tubular functional abnormalities were observed in patients with or without hypercalciuria.

A comparison of clearance and arteriovenous extraction techniques for measurements of renal hemodynamic functions.

No previous studies have directly compared timed urine collections (UV/P) vs. arteriovenous (A-V) extraction methods for determination of renal function in whole kidney preparations. We examined different markers and techniques for assessing renal plasma flow (RPF), filtration fraction (FF), and glomerular filtration rate (GFR) in both steady-state and rapidly changing conditions following 2 ml/kg bolus intravenous injections of either Renografin 76% (meglumine/sodium diatrizoate-76%) or hypertonic mannitol 25%. During steady-state conditions, excellent correlations were obtained when comparing markers and techniques. Thus, timed urinary clearances of inulin vs. 99m-technetium DTPA (Tc) had a correlation coefficient (R) of .96 (P less than .01; n = 16), and the A-V extraction technique of inulin vs. Tc as determinants of GFR showed a correlation of R = .98 (P less than .01; n = 15). The timed urinary clearance of inulin vs. the A-V extraction of inulin for glomerular filtration gave a correlation of R = .93 (P less than .01; n = 15). The clearance of para-aminohippurate (PAH) divided by the extraction of PAH vs. flow determinations using the electromagnetic flowmeter gave a correlation of R = .92 (P less than .01; n = 16). The anticipated decrease in GFR following contrast medium and hypertonic mannitol was observed using the A-V extraction technique, whereas an artifactual, exaggerated increase in GFR was observed using the timed urine collection technique. Similarly, we noted an exaggerated increase in RPF using CPAH/EPAH as the methodology. We conclude that rapid changes in renal hemodynamics may be measured accurately using the A-V extraction technique but not with clearance techniques requiring timed urine collections.

Acute systemic and renal hemodynamic effects of meglumine/sodium diatrizoate 76% and iopamidol in euvolemic and dehydrated dogs.

We examined the acute systemic and renal hemodynamic effects of intravenous meglumine/sodium diatrizoate-76% and iopamidol in euvolemic and dehydrated dogs. The physiologic responses were compared with acute changes in the level of an endogenous heparin-like material (EHM). One of eight dehydrated dogs receiving diatrizoate (2 ml/kg) had an immediate vomiting reflex associated with a very significant decline in all measured renal hemodynamic parameters; none of eight dehydrated dogs receiving iopamidol experienced a similar reaction. EHM levels did not correspond to the magnitude of the physiologic responses following either iopamidol or diatrizoate. Significant differences between iopamidol and diatrizoate were noted when comparing the magnitude of the decrease in systemic pressure (- delta 3.8 +/- 3.02, iopamidol, n = 8; vs. - delta 19.4 +/- 7.3 mm Hg, diatrizoate, n = 8; P less than .03), increased renal plasma flow (+ delta 6.2 +/- 4.9, iopamidol, n = 8; vs. + delta 33.7 +/- 8.0 ml/min, diatrizoate, n = 8; P less than .05), and decreased filtration fraction (- delta 0.09 +/- 0.01, iopamidol, n = 8; vs. - delta 0.14 +/- 0.02, diatrizoate, n = 8; P less than .03). There was no significant difference in the decrease in glomerular filtration rate (- delta 7.4 +/- 1.0, iopamidol, n = 8; vs. - delta 9.3 +/- 1.3, diatrizoate, n = 8; P greater than .05), since the marked drop in filtration fraction occurring with diatrizoate was counterbalanced by the marked increase in renal plasma flow. Acute systemic and renal hemodynamic effects are significantly lessened when comparing iopamidol with diatrizoate.

The influence of glucocorticoid dose on protein catabolism after renal transplantation.

Protein catabolic rate (PCR) and protein balance were measured daily by computerized mass balance studies in 20 subjects during hospitalization after renal transplantation. All hospital courses were uncomplicated. Ten subjects received approximately 1 mg/kg/day prednisone, and ten subjects received 3-5 mg/kg/day prednisone on day 1 with a tapering dose to approximately 1 mg/kg/day by discharge. In both groups, PCR rose during the first 3-4 postoperative days then stabilized at an accelerated level. PCR was significantly greater in the higher prednisone group. Despite encouragement most subjects ate less protein than prescribed, and most were in negative protein balance. Mean daily and net protein deficits were more severe in the higher prednisone group. Higher protein intakes improved protein balance. The protein catabolic effects of the two regimens have been defined and a dose dependency demonstrated. In any therapeutic situation the use of the minimum effective dose of steroids seem advised, and high protein intake should be encouraged to improve protein balance. Some steroid morbidity might thus be avoided.

Effects of contrast media on renal function and subcellular morphology in the dog.

The effects of intravenous contrast media (CM) on renal excretory function and subcellular morphology are examined in this animal investigation. A decrease in GFR (12.0 +/- 1.6 vs. control 30.2 +/- 2.5 ml/min) was observed when renal function was evaluated by means of the artero-venous extraction method with Tc99m DTPA and the anticipated inverse relationship to urinary flow (Vml/min) noted. An artifactual increase in GFR (43.5 +/- 10.0 vs. control 39.1 +/- 3.8 ml/min) was observed using the timed urinary clearance of inulin. V(ml/min) increased four-fold (0.6 +/- 0.16 control vs. 2.7 +/- 0.7 ml/min; P less than .05) over the first five minutes after injection of CM. Urine osmolality initially approached isotonicity and then returned toward preinjection values. Osmolal clearance (Cosm) rose 2.5 times (1.4 +/- 0.3 control vs. 3.7 +/- 1.0 ml/min; P less than .05). The fractional excretion of both Na+ (FENa+) and K+ (FEK+) increased. A comparison of urinary osmolality vs. time after injection of CM confirms a nonspecific osmotic effect on tubular (and hence total urine) flow. The hemodynamic effects of CM on the kidney via the i.v. route reflect a predominant and nonspecific osmotically mediated vasodilation. No significant light or electron microscopic changes were observed. These findings suggest that the major renal physiologic actions of hypertonic CM are a nonspecific response to agent osmolality.

Prediction of kidney mercury content by isotope techniques.

A 61-year-old female patient accidentally aspirated liquid mercury during a medically ordered diagnostic procedure. To develop animal-based guidelines, liquid mercury was introduced into the lungs of four dogs. Based on the study of these animals, a method of predicting the kidney inorganic mercury burden was developed using radioactive isotope dilution techniques. It was further demonstrated in dogs that oral administration of dimercaptopropane sulfonate (DMPS) increased mercury excretion and reduced the kidney burden. A rat experiment was performed permitting a statistical evaluation of the assumptions basic to the use of the method. The method was applied to the patient with the result that the kidney inorganic mercury burden was predicted to be 28.1 mg, 8 months after the accident. Treatment with DMPS increased urinary excretion and the post-treatment kidney burden was estimated at 19.6 mg Hg. Inasmuch as the radioactive dose to the subject may be kept at a negligible level and because sensitive methods exist for measurement of radioactive and stable mercury concentrations, the technique may be applicable in special cases to the estimation of kidney inorganic mercury burdens incurred by industrial exposure.

Protein catabolism during the postoperative course after renal transplantation.

Protein catabolic rate (PCR) was measured daily by computerized mass balance studies in 50 subjects during hospitalization after renal transplant. All subjects received 60 mg prednisone per day. PCR rose over the first 3 to 4 postoperative days and then stabilized at an accelerated level, which was sustained through the third posttransplant week. Rejection therapy with either 3 mg/kg/d prednisone or 15 mg/kg/d of methylprednisolone for 3 days further increased PCR, but there was no difference in PCR between these two regimens. Protein restriction did not decrease PCR and subjects offered a higher protein diet did not have further acceleration of PCR. We conclude that 60 mg/kg/d prednisone produces an obligatory acceleration of PCR that is further accentuated by higher steroid doses. The use of minimal maintenance doses of prednisone consistent with adequate immunosuppression seems wise. Protein balance may be improved if protein intake is increased to match individual rates of accelerated protein catabolism.

Renal threshold phosphate concentration in patients with idiopathic nephrolithiasis: correlations with tubular functions, serum parathyroid hormone and 1,25(OH)2D3.

The renal handling of inorganic phosphate was measured in 17 idiopathic nephrolithiasis patients with normal glomerular filtration rate and effective renal plasma flow. TmPO4/GFR was less than 2.5 mg/dl in nine subjects (Group I) and greater than or equal to 2.5 in eight (Group II). The former had serum PO4 of 2.5 +/- 0.13 mg/dl and the latter, 3.5 +/- 0.11 mg/dl (p less than 0.01). Four in Group I and five in Group II were hypercalciuric. There was no significant difference in the serum parathyroid hormone and 1,25(OH)2D3 between the two groups. However, renal tubular functions were abnormal in both groups. The low TmPO4/GFR in 53 per cent of the patients is another manifestation of tubular functional abnormality seen in idiopathic nephrolithiasis.