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Kidney injury is a common finding in patients with liver disease. Bile cast nephropathy (also known as cholemic nephropathy) is an overlooked cause of renal injury in patients with hyperbilirubinemia. It can occur as a result of the toxic effects of bilirubin and bile acids on the renal tubules via several mechanisms. Bile cast nephropathy has characteristic histopathological changes consisting of bilirubin cast deposition in the distal nephron along with tubular epithelial cell injury. Treatment is based on the reversal of liver injury. This review aims to describe bile cast nephropathy in terms of its clinical and morphological features and to shed light on diagnostic techniques. In addition, we present data on management of such nephropathy while reviewing all the reported cases of bile cast nephropathy.

We studied the characteristics of the basal and antidiuretic hormone (arginine vasotocin, AVT)-activated whole cell currents of an aldosterone-treated distal nephron cell line (A6) at two different cytosolic Ca2+ concentrations ([Ca2+] c , 2 and 30 nm). A6 cells were cultured on a permeable support filter for 10 ∼ 14 days in media with supplemental aldosterone (1 μm). At 30 nm [Ca2+] c , basal conductances mainly consisted of Cl− conductances, which were sensitive to 5-nitro-2-(3-phenylpropylamino)-benzoate. Reduction of [Ca2+] c to 2 nm abolished the basal Cl− conductance. AVT evoked Cl− conductances at 2 as well as 30 nm [Ca2+] c . In addition to Cl− conductances, AVT induced benzamil-insensitive nonselective cation (NSC) conductances. This action on NSC conductances was observed at 30 nm [Ca2+] c but not at 2 nm [Ca2+] c . Thus, cytosolic Ca2+ regulates NSC and Cl− conductances in a distal nephron cell line (A6) in response to AVT. Keeping [Ca2+] c at an adequate level seems likely to be an important requirement for AVT regulation of ion conductances in aldosterone-treated A6 cells.

Autosomal dominant distal renal tubular acidosis (ddRTA) is caused by mutations in SLC4A1, which encodes the polytopic chloride-bicarbonate exchanger AE1 that is normally expressed at the basolateral surface of alpha-intercalated cells in the distal nephron. Here we report that, in contrast with many disorders in which mutant membrane proteins are retained intracellularly and degraded, ddRTA can result from aberrant targeting of AE1 to the apical surface.

In acute interstitial nephritis (AIN), mononuclear cells invade the tubules (tubulitis). The segmental localization of tubulitis is not precisely known. To clarify this question, formalin-fixed kidney biopsy specimens from 13 patients with AIN were studied stereologically by identifying cortical tubules with segment-specific markers. The periodic acid-Schiff reaction, peanut lectin, and antibodies against Tamm-Horsfall protein and epidermal cytokeratins all applied to the same section were used to identify the proximal tubules (PTs), distal convoluted tubules, distal straight tubules, and the cortical collecting system (connecting tubules and cortical collecting ducts), respectively. Morphometrically, an estimate of the relative volume of the inflammatory cell infiltrates within each category of tubular segments was obtained. Inflammatory cells were infrequently found in PTs (1.2%) but were frequently localized in distal tubules and the cortical collecting system (7.6%). There was no difference in the amount of the inflammatory cell infiltrate within these segments. Re-examination of an electron microscopic study of AIN carried out in this laboratory revealed that mononuclear cells were rarely seen in convoluted PTs but were frequently observed in straight PTs and all segments distal to them. The observations indicate that it is the distal nephron which is primarily affected by inflammatory cell infiltration in AIN.

The histo- and cytogenesis of two cases of renal oncocytoma have been studied by cytomorphological and cytochemical methods. Transitions from collecting ducts into oncocytic tubules were observed at the light and electron microscopic levels. The fine structure of the oncocytes in tubules and tumors is described in detail. Cytochemically, the oncocytic tubules and oncocytomas share many characteristics with the distal nephron, especially the collecting ducts. A striking difference is the enhanced activity of succinic dehydrogenase which corresponds to the increase in the number of mitochondria in oncocytes. All the results suggest that renal oncocytoma originates from the collecting duct.

Five patients who developed hypomagnesaemia, hypokalaemia, and hypocalcaemia in association with Tobramycin therapy are described. In all cases the proximate lesion of the disorder appeared to be a defect of magnesium conversion by the distal nephron. Onset of tetany led to detection of the syndrome in three patients (two of whom also had ventricular arrhythmias), but two were asymptomatic and detected only by biochemical screening. Spontaneous resolution occurred in all cases within four to twenty-one days (mean ten days) during which time intensive biochemical monitoring and support were required to prevent recurrence.

Micropuncture studies demonstrate phosphate reabsorption in proximal tubules and between the late proximal and early distal convoluted tubule accessible to micropuncture. To further define the sites of phosphate reabsorption, the stationary microperfusion technique was applied to proximal and distal nephron segments. Phosphate reabsorption was evaluated in superficial loops of proximal tubules, descending segments beyound late proximal tubules accessible to micropuncture, ascending segments up to the point of micropuncture in the distal tubule, and superficial loops of distal tubules of thyroparathyroidectomized rats. Microperfusates of 1.3 or 2.6 nl (100 mmol/1 mannitol, 100 mmol/l NaCL, 32P-phosphate and 3H-inulin) were injected and then withdrawn after contact times of 2--108 s. Phosphate recovery relative to that of inulin was determined. A steep exponential decline of phosphate recovery (R) iwth increasing contact time (t) was observed in the superficial proximal tubule and descending segments. The slopes of the logarithmic regressions (10log R)/t, +/- SEM) were: -1.68 +/- 0.33 and -1.21 +/- 0.24min-1 in superficial proximal tubules and descending segments respectively. In contrast, no significant decline in phosphate recoveries (-0.02 +/- 0.04 and + 0.11 +/- 0.10 min-1) was apparent in the ascending segments and distal tubule. It is concluded that phosphate is reabsorbed in the proximal convoluted tubule and adjacent descending segments of the superficial nephron and that there is no significant phosphate reabsorption in distal convoluted tubules and adjacent ascending segments.

Epithelia can be classified as "leaky" and "tight epithelia" due to their conductive properties and their modes of solute transport. Both the proximal segment of the nephron and the intestinal tract are "leaky" whereas the distal nephron and the colon are "tight". Consequently, inborn errors and exogenous disorders of solute transport often involve both the proximal tubule and the small intestine. In addition, effects on ion and water transport in the distal nephron closely resemble those in the large intestine. Models of solute transport in leaky and tight epithelia are presented employing porter systems known in mammalian tissues. These porter systems are discussed as possible sites of transport defects and as targets for pharmacological agents.

Angriffspunkt und Wirkungsmechanismus von Furosemid wurden am Menschen unter den Bedingungen der forcierten Wasserdiurese und der osmotischen Diurese untersucht. Wahrend einer Wasserdiurese stieg das Harnzeitvolumen nach Furosemid intravenos kurzfristig bis auf 40% des Glomerulusfiltrates an, so das zunachst ein proximaltubularer Angriffspunkt vorliegt. Gleichzeitig nahm CH2O unmittelbar nach Furosemid intravenos trotz Zunahme von Cosm erheblich ab, d.h. es kam zu einer weitgehenden Hemmung des Natriumtransportes auch im distalen Nephron zwischen aufsteigendem Schenkel der Henleschen Schleife und Sammelrohren. Unter osmotischer Diurese (10% Mannitol) wurde TmcH2O durch Furosemid bis auf Null reduziert und die effektive Nierengesamtdurchblutung um durchschnittlich 27% erhoht. Diese Befunde bei gleichzeitiger Zunahme der Kaliurese sprechen fur eine Hemmung des Natriumtransportes im aufsteigenden eines hypotonen Diuresezuwachses zeigt — nicht komplett sein kann. Daneben ist eine partielle „Auswaschung“ des medullaren Natriumpool im Rahmen der gesteigerten Nierengesamtdurchblutung moglich.

These studies were designed to determine whether the effect of CPUO on the renal tubule is dependent upon the pattern of transport prevailing at various stages of development. Guinea pigs (n=78) underwent CPUO at birth, 1,2,3 or 4 wks of life and were studied 4 wks later (E). Sham operated littermates served as controls (C). The degree of CPUO, measured by the resistance to a constant flow of fluid, was similar in all groups. TRP averaged 87% in C, was slightly lower in the contralateral kidney (CK) of E (82%) and did not vary with age, whereas it increased with age (p 0.9) in AK at all ages. UV (μl/min/100 ml GFR) of the AK was 22.4 ± 3.7 when surgery was performed at birth, 26.7 ± 4.0, when surgery was done at 1 wk, and then decreased rapidly to reach 5.8 ± 1.2 when CPUO was produced at 4 wks (p