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Biomedical subjects

R E Cronin

Publications and source records attributed to R E Cronin.

At least 37 records · Page 2Linked to original sources
PubMed1982

Renal cortex ion composition and Na-K-ATPase activity in gentamicin nephrotoxicity.

Abnormalities of potassium and magnesium homeostasis have been reported following the use of gentamicin, and potassium depletion enhances gentamicin nephrotoxicity. The present study investigates these relationships in the dog by assessing changes in renal cortex ion composition and renal cortex Na-K-ATPase activity occurring during gentamicin nephrotoxicity. Gentamicin (15 mg/kg i.m. twice daily) was administered for 4 to 7 days to potassium-depleted or potassium-supplemented animals. The results show that gentamicin nephrotoxicity was characterized by a significant reduction in renal cortex content of potassium (17%), magnesium (19%), and phosphorus (12%) in all groups of animals given gentamicin. However, only potassium-depleted animals exposed to 7 days of gentamicin experienced a significant rise in plasma creatinine (from 1.3 +/- 0.1 to 4.3 +/- 1.0 mg/dl). Accompanying this increase in plasma creatinine was a significant rise in the renal cortex content of sodium (from 25 +/- 0.5 to 27.9 +/- 1.7 meq/100 g fat-free dry solid wt) and calcium (from 1.2 +/- 0.1 to 2.6 +/- 0.3 mM/100 g fat-free dry solid wt). Na-K-ATPase activity in the renal cortex fell only in potassium-depleted animals after 4 days (from 11.5 +/- 0.9 to 7.8 +/- 0.1 microM Pi.mg protein-1.h-1) and 7 days (5.9 +/- 0.8 microM Pi.mg protein-1.h-1) of gentamicin treatment. Thus, gentamicin nephrotoxicity is characterized by sequential changes in renal cortex ionic composition, sodium pump activity, and renal function.

Animals↗
PubMed1982

Skeletal muscle injury after magnesium depletion in the dog.

Magnesium deficiency was induced in a setting of an otherwise adequate diet in adult beagle dogs. Despite the development of severe hypomagnesemia (from 1.5 +/- 0.2 to 0.5 +/- 0.2 meq/liter) during the 10-wk study, Mg content of skeletal muscle fell only modestly (from 3.8 +/- 0.2 to 3.1 +/- 0.4, P less than 0.005, at 7 wk and 3.5 +/- 0.4 mM/100 g FFDS, NS, at 10 wk). The most pronounced muscle compositional changes were a loss of phosphorus (from 29.5 +/- 1.8 to 22.0 +/- 1.6, P less than 0.001, at 7 wk and 24.8 +/- 2.8 mM/100 G FFDS, P less than 0.001, at 10 wk) and gains of calcium (from 0.64 +/- 0.11 to 0.93 +/- 0.17, P less than 0.05, at 7 wk, and 0.85 +/- 0.26 mM/100 g FFDS, P less than 0.05, at 10 wk), sodium (from 13.2 +/- 2.6 to 22.9 +/- 4.7, P less than 0.001 at 7 wk and 17.8 +/- 2.0 meq/100 g FFDS, P less than 0.005, at 10 wk), and chloride (from 5.8 +/- 0.8 to 8.2 +/- 1.6, P less than 0.001, at 7 wk and 6.8 +/- 0.6 meq/100 g FFDS, P less than 0.05, at 10 wk). Cellular potassium content did not change (from 35.9 +/- 1.9 to 33.0 +/- 4.1, NS, at 7 wk and 36.3 +/- 2.0 meq/100 g FFDS, NS, at 10 wk). Muscle cell electrical hyperpolarization developed after 10 wk of Mg depletion. Convulsive seizures developed in three animals. Frank rhabdomyolysis in three animals and focal necrosis in four animals were present on terminal biopsy, with only four animals having completely normal histology.

Animals↗
PubMed1982

Dissociation of systemic and renal effects in endotoxemia. Prostaglandin inhibition uncovers an important role of renal nerves.

To elucidate the mechanisms responsible for systemic and renal hemodynamic changes in early endotoxemia, the roles of prostaglandins (PG) and renal nerves were investigated. Endotoxin (E, 3 micrograms/kg i.v.) was given to two groups of anesthetized dogs that had undergone unilateral renal denervation: Group I (n = 9) E only; Group II (n = 11) E + indomethacin (10 mg/kg i.v.) or meclofenamate (5 mg/kg i.v.). A third group of dogs (Group III, n = 5) received indomethacin (10 mg/kg i.v.) only. 1 h after E group I dogs, mean arterial pressure (MAP) decreased from 126 to 94 mm Hg (P less than 0.001), and prostacyclin (6-keto-Fl alpha metabolite, PGI2) increased (from 0.64 to 2.08 ng/ml, P less than 0.005). Glomerular filtration rate (GFR) and renal blood flow (RBF) declined comparably both in innervated and denervated kidneys. In marked contrast, group II dogs had a stable MAP (136-144 mm Hg, NS) and no increase in PGI2 levels. Plasma renin activity (0.7-2.5 ng/ml per h, P less than 0.005) increased, and renin secretion was greater in innervated compared with denervated kidneys (255 vs. 74 U/min, P less than 0.01) in these PG-inhibited dogs. In addition, denervated kidneys in group II dogs had a greater GFR (42 vs. 34 ml/min, P less than 0.01) and RFB (241 vs. 182 ml/min, P less than 0.01) than innervated kidneys after E. Group III animals had no significant changes in systemic or renal hemodynamics, plasma renin activity or PGI2 during the study. These results suggest that PGI2 mediates the systemic hypotension of early endotoxemia in the PG-intact animal. Moreover, PG inhibition uncovers an important effect of E to increase efferent renal nerve activity with a consequent decline in GFR and RBF independent of changes in MAP. Finally, the results demonstrate that renal nerves are important stimuli to renin secretion in early endotoxemia via pathways that are PG-independent.

Animals↗
PubMed1982

Effect of potassium depletion on tubular morphology in gentamicin-induced acute renal failure in dogs.

Potassium deprivation has recently been reported to potentiate the degree of functional impairment in a gentamicin-induced model of acute renal failure. The present study investigated the effects of two different states of potassium homeostasis on the development of cellular injury in the early stage of gentamicin nephrotoxicity in dogs. Gentamicin (15 mg. per kg. intramuscularly twice daily) was administered for 4 and 7 days to potassium-depleted or potassium-supplemented animals. The results show that potassium supplementation markedly lessens the severity of pathologic alterations induced by gentamicin. In both groups of animals, the S1 and S2 segments of the proximal tubule were the most consistently damaged regions of of the nephron. Potassium-supplemented dogs had a significantly higher number of normal proximal tubule cells than did the animals deprived of potassium and viewed 7 days after gentamicin treatment (77.3 versus 36.9 per cent; p less than 0.025). The degree of total injury to the proximal tubule was significantly higher in potassium-depleted animals than in those supplemented with potassium (59.9 versus 21.9 per cent; p less than 0.05). Only those dogs depleted of potassium prior to the administration of gentamicin had a markedly elevated plasma creatinine level of proximal tubular injury and functional impairment (r = 0.81; p less than 0.005). Potassium supplementation appears to lessen the extent of structural alterations seen in this model of gentamicin-induced acute renal failure in dogs.

Acute Kidney Injury↗
PubMed1981

The influence of circulating catecholamines and prostaglandins on canine renal hemodynamics during hemorrhage.

The relationship between circulating catecholamines and prostaglandins and the independent contribution of circulating catecholamines to renal vasoconstriction during hemorrhage is unknown. The renal hemodynamic effects of a 30% decrease in blood pressure by hemorrhage were therefore studied in three groups of anesthetized dogs which had undergone prior bilateral renal denervation. A constant unilateral infusion of the catecholamine antagonist phenoxybenzamine (POB, 0.2 micrograms/kg per min) into the renal artery during hemorrhage was also performed. In the control (C) dogs (n = 6), hemorrhage was not associated with significant changes in glomerular filtration rate (GFR) or renal blood flow (RBF) in either POB-infused and denervated or noninfused, denervated kidneys. In the second group of dogs (n = 8), pretreated with the prostaglandin inhibitor indomethacin (IN, 10 mg/kg, iv), POB-infused and denervated kidneys had a significantly higher GFR (30 vs. 23 ml/min, P less than 0.05) and RBF (180 vs. 130 ml/min, P less than 0.0-5) than contralateral denervated kidneys during the hemorrhage period. Similar results were observed in the third group of dogs (n = 6) pretreated with the chemically dissimilar prostaglandin inhibitor meclofenemate (M). Circulating plasma catecholamines increased to a similar degree in C (116 to 530 pg/ml, P less than 0.005), IN (116 to 488 pg/ml, P less than 0.005), and M (75 to 315 pg/ml, P less than 0.01) groups; the major part of this increase was due to an increase in plasma norepinephrine (NE). These results indicate that, in this model of hemorrhage, plasma NE exerts a moderate but significant renal vasoconstrictor effect which is unmasked by prostaglandin inhibition.

Animals↗
PubMed1981

Recovery from rapidly progressive glomerulonephritis. Improvement after plasmapheresis and immunosuppression.

Two patients with rapidly advancing renal insufficiency underwent biopsy and were found to have crescentic glomerulonephritis. Patient 1 demonstrated findings compatible with Goodpasture's syndrome. Crescents were present in 100% of his glomeruli. Patient 2 had findings of immune complex-mediated glomerulonephritis and crescents in greater than 90% of his glomeruli. Both patients were treated with high-dose prednisone, cyclophosphamide, and plasmapheresis. Patient 2 additionally required hemodialysis for a brief period. Renal function improved in both patients and has not deteriorated after follow-up of 14 and 18 months, respectively. Repeated renal biopsies were performed in each patient. Our findings suggest that clinical improvement and histologic healing are possible in rapidly progressive glomerulonephritis despite the initial presence of crescents in every glomerulus.

Adult↗
PubMed1980

Glomerular architectural changes after a two-hour infusion of norepinephrine.

Alterations in glomerular architecture have been suggested to play a role in the pathogenesis of several models of acute renal failure. In this study, mongrel dogs were subjected to an intrarenal infusion of norepinephrine for 2 hours. Light microscopy and scanning and transmission electron microscopy were used to describe glomerular architecture 2 days after the initial norepinephrine infusion. In addition, scanning electron microscopy was used to quantitate the percentage of "abnormal areas" in glomerular capillary-loop morphology in both norepinephrine-infused kidneys and the contralateral control kidneys. Alterations in glomerular structure in these experiments appeared to be much less extensive than previously reported. A variable amount of glomerular pedical shape simplification was seen, which involved about 15% of the capillary loop. Quantitative evaluation revealed abnormal morphology of 15.2% +/- 0.6% of the glomerular capillary loop in the norepinephrine-infused kidneys, compared to 2.9% +/- 0.4 abnormal loop structure in the contralateral control kidneys (P less than 0.001). It is concluded that alterations in glomerular structure are not extensive in this model.

Acute Kidney Injury↗
PubMed1980

Role of osmolality in blood pressure stability after dialysis and ultrafiltration.

To clarify the mechanisms involved in the stability of blood pressure during ultrafiltration (UF) alone versus regular dialysis, this study systematically examined the importance of changes in serum potassium, osmolality, and plasma norepinephrine during several dialysis maneuvers. Six stable, normotensive chronic dialysis patients were subjected to a uniform 2 to 3% decrease in body weight during the 2 hours of each dialysis maneuver. Supine to upright mean blood pressure (MBP) decreased (90 to 75 mm Hg, P less than 0.05), and three patients became symptomatic after weight loss during regular dialysis, but orthostatic blood pressure was stable (89 to 86 mm Hg, NS) and the patients were asymptomatic after UF and weight loss. Isokalemic regular dialysis did not afford hemodynamic stability, as orthostatic MBP declined (85 to 56 mm Hg, P less than 0.02), and four of the patients were again asymptomatic after standing. A continuous hypertonic mannitol (25%) infusion during the 2-hour dialysis, however, kept osmolality from decreasing and was associated with a stable orthostatic MBP (89 to 83 mm Hg, NS). A continuous infusion of isotonic mannitol (5%) given in a volume of five times that of the hypertonic mannitol failed to prevent orthostatic hypotension (80 to 60 mm Hg, P less than 0.005). Plasma norepinephrine concentrations were high in these patients and increased only modestly after weight loss. These results implicate constant plasma osmolality as a critical protective factor of blood pressure during UF and further demonstrate that changes in blood pressure may be associated from changes in both serum potassium and plasma norepinephrine concentration.

Blood↗
PubMed1980

Ischemia and tubule obstruction during acute renal failure in dogs: mannitol in protection.

The pathogenetic factors involved in norepinephrine- (NE) induced reversible acute renal failure (ARF) were examined in untreated (U) and mannitol-treated (M) animals. At 3 and 24 h after NE infusion renal blood flow (RBF) was significantly higher in M compared to U animals (174 vs. 138 and 191 vs. 148 ml/min, respectively, both P less than 0.05). At 3 h, glomerular filtration rate (GFR) was higher in M animals (8 vs. 4 ml/min, P less than 0.01), while at 24 h protection was even greater (18 vs. 3 ml/min, P less than 0.01). In U animals proximal tubule pressure (Pt) was lower at 1 h than before NE (13 vs. 23 mmHg, P less than 0.01); from 1 to 3 h Pt increased to elevated levels in parallel with restoration of RBF (r = 0.62, P less than 0.01). At 3 h in U animals stop-flow pressure (SFP), as an index of glomerular capillary pressure, was below normal (35 vs. 44 mmHg, P less than 0.05) yet Pt was increased (35 vs. 23 mmHg, P less than 0.05). Thus little transglomerular pressure gradient was present for ultrafiltration. Further evidence of tubular obstruction was obtained by microperfusion at 6 nl/min, which increased Pt from 30 to 45 mmHg (P less than 0.001), a finding not present in unobstructed tubules. Delayed excretion (approximately 20 min) of microinjected [3H]inulin also was compatible with renal ischemia and tubule obstruction. Microinjection studies provided no evidence for backleak of tubular fluid. At 1 h, Pt was higher in M vs. U animals (31 vs. 13 mmHg, P less than 0.05). In M animals at 3 h SFP was normal (50 vs. 44 mmHg) and Pt was below SFP (32 vs. 50 mmHg, P less than 0.01), thus preserving a substantial transglomerular pressure gradient for ultrafiltration. In summary, reduced GFR in U animals is characterized by a combination of reduced glomerular capillary pressure and tubule obstruction. In contrast, animals receiving mannitol were protected against ARF through maintenance of glomerular capillary pressure and prevention of tubular obstruction, perhaps by increasing Pt within the first hour of the NE insult.

Acute Kidney Injury↗
PubMed1980

Natural history of aminoglycoside nephrotoxicity in the dog.

The natural history of aminoglycoside nephrotoxicity is not well described. This study investigated in the dog renal functional and electrolyte abnormalities during and for 20 days following a 10-day course of low-dose gentamicin (7 mg/kg/day), high-dose gentamicin (30 mg/kg/day), and netilmicin (30 mg/kg/day). Renal histology was examined at the end of the study. Renal functional abnormalities occurred only in animals receiving high-dose gentamicin. A fall in maximal urinary osmolality (1579 +/- 347 mOsm/kg/H2O to 450 +/- 118, p less than 0.05) was followed by renal glycosuria and a fall in GFR (66.9 +/- 11.9 ml/min to 21.3 +/- 8.6, p less than 0.05). These three functional indices had recovered by day 30 in the survivors. Plasma potassium fell in animals receiving high-dose gentamicin (3.8 +/- 0.02 mEq/L to 3.3 +/- 0.4, p less than 0.05) and reached the lowest values (2.7 and 2.9 mEq/L) just prior to death in two animals dying in uremia. Netilmicin also caused a significant fall in plasma potassium (4.3 +/- 0.1 mEq/L to 3.9 +/- 0.1, p less than 0.05). Hypocalcemia (10.0 +/- 1.3 mg/dl to 7.8 +/- 1.4, p less than 0.05) but not hypomagnesemia developed following high-dose gentamicin. Peak serum aminoglycoside levels after high-dose gentamicin and netilmicin were comparable, but trough levels rose only in high-dose gentamicin animals and paralleled the fall in GFR. Light microscopy of the kidney 3 weeks after high-dose gentamicin demonstrated no proximal tubular necrosis but extensive focal tubulointerstitial nephritis, especially in the juxtamedullary cortex. Similar but less extensive derangements were noted in animals receiving low-dose gentamicin, despite the absence of functional abnormalities. Minor histological abnormalities were noted in animals receiving netilmicin. To summarize: 1) major renal functional and electrolyte abnormalities developed only following high-dose gentamicin and included impaired urinary concentration, glycosuria, reduced GFR, hypokalemia, and hypocalcemia (except for a fall in plasma potassium, similar doses of netilmicin were not nephrotoxic); (2) tubulointerstitial nephritis, particularly in the juxtamedullary cortex, occurred with low-dose gentamicin as well as high-dose gentamicin and may be a factor in delayed or incomplete recovery from gentamicin nephrotoxicity; (3) in this model, netilmicin at comparable doses was substantially less nephrotoxic than gentamicin; (4) renal postassium wasting may be a heretofore unrecognized consequence of aminoglycoside administration.

Animals↗
PubMed1979

Survey of the morphology of the dog kidney.

Dogs are frequent subjects in experimental studies of renal physiology and pathology in spite of the paucity of information on their normal renal morphology. In this study, gross morphology, light microscopy, and scanning and transmission electron microscopy were used to describe dog renal anatomy. The dog has a multilobed kidney with the medulla fused into an elongate crest and a renal pelvis of elaborate shape. The outer zone of the medulla lacks a definitive outer stripe. The proximal tubule consists of four distinct anatomical segments. Dark cells are abundant in the collecting duct of the inner medulla. The majority of the nephron segments demonstrate remarkable similarities to those of the human kidney and less to those of the kidney of the laboratory rat.

Animals↗
PubMed1979

Aminoglycoside nephrotoxicity: pathogenesis and prevention.

Nephrotoxicity resulting from aminoglycoside antibiotics is a serious clinical problem and the incidence is probably increasing. The mechanism of renal toxicity is unclear but these agents affect several nephron functions including glomerular filtration, proximal tubular reabsorption, and urinary concentration. The degree of toxicity appears to correlate with the level of renal tissue concentration of aminoglycoside. Clinical nephrotoxicity is most likely to occur in the presence of volume depletion, advancing age, preexisting renal dysfunction and exposure to other nephrotoxins. Despite the use of dosing nomograms, nephrotoxicity still occurs in some patients and the decline in renal function may only become apparent after completion of the antibiotic course. Subclinical nephrotoxic effects from aminoglycosides probably occur in all patients treated with these agents and only the most severely affected have clinically apparent nephrotoxicity.

Acute Kidney Injury↗
PubMed1978

Norepinephrine-induced acute renal failure: a reversible ischemic model of acute renal failure.

The present study has defined conditions whereby a reversible form of ischemia-induced ARF can be produced in the dog. Unlike previous studies [9-11] which examined the acute phase of NE-induced ARF, this study demonstrates the feasibility of using the model for the longitudinal study of ARF. Such a model may be useful in studying the pathologic and physiologic changes which occur during different phases of ARF. Perhaps most important, this model should also provide a setting in which treatment measures, either prophylactic or therapeutic for ARF, can be examined.

Acute Kidney Injury↗
PubMed1978

Pathogenic mechanisms in early norepinephrine-induced acute renal failure: functional and histological correlates of protection.

The present study investigated the protective effect of acute volume expansion (25%) with isotonic saline, isotonic mannitol, and hypertonic mannitol in a model of unilateral norepinephrine-induced acute renal failure (ARF). Three hours following a 40-min intrarenal infusion of norepinephrine (NE) (0.75 microgram/kg/min), inulin clearance had fallen from a control value of 54.1 +/- 6.5 to 1.3 +/- 1.3 ml/min in untreated dogs and fell similarly (P = NS) to 3.3 +/- 1.5 ml/min in animals preexpanded with 0.9% saline (0.75 ml/kg/min). In contrast, as compared to the untreated animals, inulin clearance 3 hr post NE infusion was significantly greater in dogs preexpanded with 5% mannitol (9.2 +/- 2.5 ml/min, P less than 0.01), or 20% mannitol (16.6 +/- 3.9 ml/min, P less than 0.01). The protective effects of 5% and 20% mannitol were not statistically different from each other. Recovery of renal excretory function in all groups, expressed as 3-hr post NE inulin clearance, correlated with the magnitude of pre NE solute excretion rate (r = 0.612, P less than 0.001) and osmolar clearance rate (r=0.593, P less than 0.001), but not with pre insult inulin clearance (r = 0.233, P = NS) or renal blood flow (r = 0.249, P = NS). In the presence of a profound fall in inulin clearance, proximal tubular (PT) pressures in untreated dogs 3 hr post NE infusion achieved a value equal to control (26 +/- 11 vs. 25 +/- 2 mm Hg). In contrast, pretreatment with isotonic mannitol produced a rise in PT pressure both before (45 +/- 4 mm Hg, P less than 0.05) and 3 hr post NE infusion (38 +/- 5 mm Hg, P less than 0.05). In all groups of animals, at both 3 and 24 hr post NE, tubular injury was observed but glomerular architecture remained normal by light and electron microscopy. Conclusion. the protective effect of mannitol in this reversible model of ARF did not correlate with inulin clearance, renal blood flow, extracellular fluid (ECF) volume, ECF hypertonicity, or renal histologic changes but did correlate with the solute excretion rate. The increased PT pressures with mannitol both before and after the NE insult could contribute to the protective effect of attenuating any relative intratubular obstruction.

Acute Kidney Injury↗
PubMed1976

Renal cell carcinoma: unusual systemic manifestations.

A series of cases is presented which illustrates unusual aspects in the presentation, diagnosis, and management of renal cell carcinoma. The entire "classic triad" of flank pain, gross hematuria, and palpable mass was not present at the time of diagnosis in any of the patients. Moreover, in only three patients did the initial clinical findings raise the suspicion of renal cell carcinoma. A diagnosis of polycystic kidney disease, cardiac failure, glomerulonephritis, analgesic abuse, and perirenal hemorrhage obscured the primary diagnosis in the other five patients. In four patients the tumor was probably present from 3 to 12 years before detection. These findings emphasize that knowledge of the hematologic, humoral, immunologic and vascular abnormalities induced by this tumor may provide a clue to early diagnosis. The systematic use of excretion urography, nephrotomography, ultrasonography, renal scanning, renal arteriography and cyst puncture then may allow the accuracy of radiologic diagnosis of this tumor to approach 100%. Lastly, the therapy of choice for this tumor is radical nephrectomy. Excision of apparently solitary metastases also may sometimes be feasible. However, partial nephrectomy to remove tumor in a solitary kidney was performed in one patient to avoid the need for end-stage kidney treatment. Where nephrectomy renders the patient anephric, chronic hemodialysis and renal transplantation should be considered as potential measures to sustain life. While hormonal agents, chemotherapy, and radiation therapy sometimes provide palliation, their use generally has been disappointing.

Adenocarcinoma↗
PubMed1976

Mechanisms of portal hypertension-induced alterations in renal hemodynamics, renal water excretion, and renin secretion.

Clinical states with portal venous hypertension are frequently associated with impairment in renal hemodynamics and water excretion, as well as increased renin secretion. In the present investigation, portal venous pressure (PVP) was increased in anesthetized dogs undergoing a water diuresis. Renal arterial pressure was maintained constant in all studies. As PVP was increased from 6 to 20 mm Hg, decreases in cardiac output (2.5-2.0 liter/min, P less than 0.05) and mean arterial pressure (140-131 mm Hg, P less than 0.05) were observed. Increases in PVP were also associated with decreases in glomerular filtration rate (GFR, 40-31 ml/min, P less than 0.001), renal blood flow (RBF, 276-193 ml/min, P less than 0.001), and increases in renin secretion (232-939 U/min, P less than 0.025) in innervated kidneys. No significant change in either GFR or RBF and a decrease in renin secretion occurred with increases in PVP in denervated kidneys. To dissociate the changes in cardiac output and mean arterial pressure induced by increase PVP from the observed decreases in GFR and RBF, studies were performed on animals undergoing constriction of the thoracic inferior vena cava. In these studies, similar decreases in cardiac output and mean arterial pressure were not associated with significant changes in GFR or RBF. Increases in PVP also were associated with an antidiuresis as urine osmolality increased from 101 to 446 mosmol/kg H2O (P less than 0.001). This antidiuresis was significantly blunted but not abolished by acute hypophysectomy. In hypophysectomized animals, changes in free water clearance and urine flow were linearly correlated as PVP was increased. These studies indicate that increases in PVP result in decreases in GFR and RBF and increases in renin secretion mediated by increased renal adrenergic tone. Increased PVP is also associated with antidiuresis; this antidiuresis is mediated both by vasopressin release and by diminished tubular fluid delivery to the distal nephron.

Animals↗