Unusual adult-onset manifestation of an attenuated Bartter's syndrome type IV renal phenotype caused by a mutation in BSND.

Sir, Bartter's syndrome (BS) comprises a range of overlapping autosomalrecessive renal salt-losing phenotypes, characterized by hypocalaemicmetabolic alkalosis. The antenatal BS variant associated withsensorineural deafness (BS type IV) is caused by mutations inBSND [1]. This gene encodes barttin, an essential ß-subunitfor ClC-Ka and ClC-Kb chloride channels in basolateral membranesof     

A novel compound heterozygous ROMK mutation presenting as late onset Bartter syndrome associated with nephrocalcinosis and elevated 1,25(OH)<Subscript>2</Subscript> vitamin D levels

Bartter syndrome (BS) is a rare renal tubular disorder presenting with hypokalemic metabolic alkalosis, which is classified into five types. KCNJ1 mutations usually cause the neonatal form of BS, type II BS (OMIM 241200). However, this report concerns a female patient with a novel, compound heterozygous KCNJ1 mutation that causes late-onset BS. The unique clinical findings of this case include persistently elevated 1,25(OH)₂ vitamin D levels, possibly due to increase prostaglandin E₂ levels, and medullary nephrocalcinosis. Treatment with COX-2 inhibitors resolved her hypercalciuria and improved her height and weight; renal function remains stable and there is no progression of nephrocalcinosis.     

Stimulatory effect of insulin on tubular sodium reabsorption in normotensive subjects with a positive family history of hypertension

BACKGROUND: Insulin resistance and hyperinsulinaemia has been suggestedas a pathogenetic mechanism in hypertension. METHODS: In this investigation the renal response to insulin was studiedin normotensive subjects with a positive family history of hypertensionin two generations (n = 14), in one weight-matched (n = 11)and one lean (n = 13) control group. During hyperinsulinaemia(euglycaemic hyperinsulinaemic clamp technique) we determinedrenal haemodynamics (clearances of ⁵¹Cr-EDTA and PAH) and urinarysodium excretion. Lithium clearance was used to estimate thesegmental tubular reabsorption of sodium. RESULTS: In subjects with a positive family history of hypertension,hyperinsulinaemia did not influence renal plasma flow (RPF)or glomerular filtration rate (GFR) but urinary sodium excretiondecreased by 50%. Estimated proximal tubular sodium reabsorptionwas unaffected by insulin while estimated distal fractionalsodium reabsorption increased, P<0.01. At the end of theclamp a low-dose infusion of angiotensin II (0.1 ng/kg per min)was superimposed. GFR and RPF then decreased significantly concomitantwith urinary excretion of sodium. In control subjects hyperinsulinaemia caused an unchanged GFRin both groups, increased RPF in the lean control group and15–25% reduction in sodium excretion. No alteration wasseen in estimated proximal tubular sodium reabsorption, butestimated distal tubular sodium reabsorption increased (P<0.05)in the lean control group. Angiotensin II elicited a furtherincrease in distal fractional tubular sodium reabsorption inboth control groups (P<0.05). CONCLUSIONS: In normotensive subjects with a positive family history of hypertension,in contrast to control subjects without such history, hyperinsulinaemiacaused a marked decrease in urinary sodium excretion in presenceof unchanged RPF and GFR indicating a renal tubular effect ofinsulin located at a distal site of the renal tubules. AngiotensinII caused further sodium retention, probably due to an effecton renal haemodynamics.     

The pathogenetic significance of C5b-9 in IgA nephropathy

Renal biopsies from 20 patients with IgAN were retrospectivelystudied using monoclonal antibodies against T cells, monocytes/macrophages(MM), HLA-DR-related antigen and the C5b-9 neoantigen. GlomerularC5b-9 deposits were mainly found in the mesangial areas andshowed an association with IgA (P<0.005) and C3 deposits(P<0.001). Interstitial T cells and MM were highly correlatedwith the interstitial DR+ve cells (P<0.001 and P<0.0005respectively). Tubular C5b-9 deposition was observed on thetubular basement membranes and related to the numbers of interstitialT cells (P<0.005), MM (P<0.005) and DR+ve cells (P<0.01)as well as to the tubular DR expression (P <0.025). The severityof tubular atrophy and interstitial fibrosis showed a positivecorrelation with the interstitial T cells, MM and DR+ve cells,as well as with the intensity of tubular C5b-9 deposition (P<0.05and P<0.05 respectively). Plasma creatinine on presentationwas correlated with the numbers of interstitial T cells (P<0.05),MM (P<0.01), interstitial DR+ve cells (P<0.005), and tubularC5b-9 deposits (P<0.005). No correlation between glomerularT cells, MM, and C5b-9 deposits with plasma creatinine was seen.During follow-up, renal function deteriorated in those patientswith the more extensive tubular C5b-9 deposits In conclusion, glomerular C5b-9 deposition seems to be secondaryto the IgA and C3 deposition. In contrast, tubular C5b-9 isrelated to the numbers of interstitial T cells and MM. Activatedinterstitial mononuclear cells may lead to the tubular depositionof C5b-9, which eventually might contribute to the developmentof tubulointerstitial lesions (TIL) and renal function impairment     

Investigating the volume status before contrast nephropathy studies.

Sir, We read with great interest the original article by Drager etal. [1] about the mechanism of a protective effect of N-acetylcysteine(NAC) against contrast-induced nephropathy (CIN) in patientsundergoing elective coronary angiography. This study assessedpre- and post-radiocontrast NAC effects on specific oxidativestress and renal tubular injury markers. CIN is one of the well-recognizedrisks of coronary     

Reversible acute renal failure from gross haematuria due to glomerulonephritis: not only in IgA nephropathy and not associated with intratubular obstruction

Seven patients with acute renal failure due to gross haematuriacaused by glomerulonephritis are described. Gross haematurialasting 4–40 days led to acute impairment of renal functionof variable severity (peak plasma creatinine 1.3–12 mg/dl)and duration. While partial recovery of renal function occurredin all patients within few days, complete remission was observedonly some months later. Three patients had IgA nephropathy (2the primary form and 1 nephritis secondary to Schönlein-Henochpurpura), two patients had acute postinfectious glomerulonephritis,andtwo others had focal necrotizing (pauci-immune) glomerulonephritis.The glomerular changes seen in renal biopsy were not enoughto explain per se the renal function impairment. Tubular changes,however, were severe and consisted of tubular necrosis, erythrocytecasts, erythrocyte phagocytosis by tubular cells, accompaniedby interstitial damage (oedema, red-cell extravasation, andinflammatory infiltrates). Study of the renal biopsies by immunofluorescencerevealed retrodiffusion of Tamm-Horsfall protein into the glomerularBowman’s space, a sign of obstructed tubular flow in anycase. It is concluded that acute renal failure due to grosshaematuria in glomerulonephritic patients may not occur onlyin IgA nephropathy, as reported so far, and is not associatedwith intratubular obstruction.     

Acute reversible renal failure with macroscopic haematuria in IgA nephropathy

Macroscopic haematuria is common in IgA nephropathy, but itssignificance and influence on prognosis remains uncertain. Wecompared the clinical and pathological features of 11 adultpatients with primary IgA nephropathy who had had a renal biopsyduring or shortly after a bleeding episode. Six patients developedtransient acute renal failure (ARF) (group 1) and five did not(group 2). Patients of group 1 had a higher percentage of tubularred-blood-cell (RBC) casts (P<0.05) and of glomerular crescents(P<0.001). However, crescents were focal and involved lessthan 50% of glomeruli. Acute tubular necrosis was only presentin patients of group 1, and ARF was attributed to the acutetubular changes rather than to the glomerular lesions. Despitea prolonged duration of ARF (mean: 38 days), further outcomedid not differ in patients of both groups. We suggest that acutetubular damage and/or tubular obstruction by RBC casts shouldbe considered in any patient who develops ARF soon after a haematuricepisode.     

Synergistic renal protection by combining alkaline-diuresis with lipid peroxidation inhibitors in rhabdomyolysis: possible interaction between oxidant and non-oxidant mechanisms

BACKGROUND AND PURPOSE.: Heme-proteins, besides causing renal tubular obstruction, maycontribute to rhabdomyolysis-induced renal injury through aheme-iron-mediated lipid peroxidation process. In the presentstudy, we compared the combined therapy of a lipid peroxidationinhibitor, 21-aminosteroid (21-AS) and fluid-alkaline-mannitol(FAM) diuresis with either of them alone to determine the efficacyof the combination therapy and to delineate the roles of lipidperoxidation and cast formation. METHODS AND RESULTS.: Employing Raman spectroscopy, we confirmed in vitro the abilityof 21-AS to inhibit iron-induced fatty acid peroxidation. 21-ASwas then administered to rats developing renal failure fromglycerol-induced rhabdomyolysis. Although 21-AS inhibited rhabdomyolysis-inducedplasma and renal lipid peroxidation, renal protection was incomplete.Administration of FAM to inhibit cast formation afforded a betterrenal protection. However, when these therapies were combinedto inhibit both lipid peroxidation and cast formation, therewas a synergistic renal functional protection. This was accompaniedby a maximum inhibition of renal and plasma lipid peroxidation,as well as, renal tubular necrosis and cast formation. Comparedto combination therapy, FAM therapy alone, despite identicalvolume, was accompanied by a higher tubular necrosis and castformation. CONCLUSIONS.: That combining a lipid peroxidation inhibitor with fluid-alkalinediuresis in rhabdomyolysis further lowers renal lipid peroxidation,tubular necrosis and cast formation and synergistically limitsrenal dysfunction (i) supports a role for lipid peroxidationin the pathophysiology of rhabdomyolysis ARF, (ii) underscoresthe role of intratubular heme retention, a cause for tubularobstruction as well a source for prodigious amount of iron,likely involved in the lipid peroxidation, and (iii) raisesthe possibility of interactions between non-oxidant and oxidantmechanisms.     

Isoproterenol stimulates tubular DNA replication in mice

The ß3-adrenergic stimulant isoproterenol is a mitogenfor cultured murine proximal tubular cells. The present studywas undertaken to test whether isoproterenol has a similar effecton tubular replication in vivo. BALB/c mice were intraperitoneallyinjected with two different doses of isoproterenol in the presenceor absence of the ß_{1 + 2}-receptor antagonist propranolol.Proliferation of renal cells was evaluated by staining of tissuesections for proliferating cell nuclear antigen (PCNA). In addition,cDNA amplification for PCNA was performed in reverse-transcribedRNA isolated from renal cortex. Treatment of mice with 0.1 mg/gbody weight isoproterenol for 24 h significantly increased PCNAstaining of nuclei compared to controls. This response was completelyblocked by propranolol. There was no light-microscopic evidencethat the proliferative response was subsequent to ischaemiawith tubular necrosis. Semiquantitative cDNA amplification revealedthat isoproterenol also stimulated the RNA expression of thePCNA gene. This study shows for the first time that isoproterenoldirectly stimulates proliferation of mainly proximal tubularcells in vivo as detected by PCNA expression. Since proliferationand differentiation of tubular cells is pivotal for the recoveryof renal function in many pathophysiological situations, ß-adrenergic-mediatedmitogenesis may be important in the reparative processes surroundingtubular epithelium regeneration.     

Immunosuppressive therapy with cyclophosphamide and prednisolone in severe idiopathic membranous nephropathy

In idiopathic membranous nephropathy (IMN) immunosuppressivetherapy should be reserved for patients with potential riskfactors at baseline or who show a progressive course. Cyclophosphamidepulse therapy (CPT) in IMN is not yet widely tested. We carriedout a trial of CPT combined with conventional treatment in agroup of patients with IMN at a greater risk. The study group consisted of 36 nephrotic adult IMN patients(M, 26; F, 10) with various combinations of risk factors. Meanproteinuria was 11.3 g/day, 47.% patients were hypertensive,78% had tubular changes, and 36% had focal glomerulosclerosis.They were treated with CPT and/or conventional low-dose cyclophosphamideand prednisolone. Median duration of immunosuppression was 14months and median total cumulative dose of cyclophosphamide172mg/kg body weight. At 6 months (6m) remission was achieved in 44% cases and atthe 36th month in 73%. None of the patients developed moderateor severe renal failure. Side-effects were minimal. Multivariateanalysis of baseline data and the changing course of the diseaseduring therapy showed that tubular changes (P = 0.0025), creatinineclearance at baseline (P = 0.04) and at 6m (P = 0.02), and proteinuriaat 6m (P<0.0001) significantly influenced the therapeuticeffect. We conclude that cyclophosphamide (including pulse) and prednisolonecan bring significant remission and maintain renal functionin IMN with potential risk factors.     

Expression of receptors for advanced glycosylated end-products in renal disease

BACKGROUND: Advanced glycation endproducts (AGEs) are believed to mediatelong-term complications in diabetes mellitus. In this contextwe studied the expression of the receptor for AGEs (RAGE) inthe kidney of patients with a variety of different renal diseases. METHODS: RAGE was detected by immunocytochemistry in renal biopsies.We compared the staining for RAGE in nine patients with diabeticnephropathy, 20 with inflammatory and/or immune complex and10 with non-inflammatory renal diseases. Normal renal tissuefrom seven patients with tumour nephrectomies served as controls. RESULTS: In controls the only cells expressing RAGE constitutively wereinterstitial cells and vascular smooth muscle cells (6/7), whiledistal tubular cells were rarely positive (1/7). Endothelialcells of arteries/arterioles, glomerular endothelial cells,podocytes, and capsular epithelial cells were consistently negative. In diabetic nephropathy, inflammatory and/or immune complex,and non-inflammatory renal diseases, all cell types mentionedabove became positive for RAGE. Whilst the distribution of RAGEin the tissue was quite similar, staining intensity in inflammatoryand/or immune complex diseases was higher than in diabetic nephropathy. CONCLUSION: RAGE induction in the kidney is not specific for diabetic nephropathyand occurs in other types of renal diseases as well.     

Renal tubular responses to low-dose infusion of angiotensin II in type 1 diabetes mellitus; relation to chronic glycaemic control

Renal responses to low-dose infusion of angiotensin II (ANGII,1.25 and 2.5 ng.kg^–1 min^–1) were examined in 15patients with type 1 diabetes and in 10 control subjects afterpretreatment with lithium carbonate (750 mg, 20 mmol). Meanarterial pressure rose during ANGII infusion in both groups.The renal haemodynamic response to angiotensin II was not abnormalin the diabetic patients. Absolute proximal reabsorption ofsodium was increased at baseline in the diabetic group, andfell during ANGII. Fractional lithium excretion was reducedin the diabetic patients at baseline (P<0.05), and the fallin fractional lithium excretion during ANGII was less than inthe control group (P=0.012). In the diabetic group correlationsexisted between glycated haemoglobin and baseline glomerularfiltration rate (P<0.05), baseline fractional lithium excretion(P=0.03), and the fall in fractional lithium excretion duringangiotensin II infusion (P=0.013). There was no correlationbetween glycated haemoglobin and absolute lithium clearance.Some indices of sodium reabsorption by the proximal renal tubulein diabetic patients correlate with prevailing chronic glycaemiccontrol, largely reflecting changes in glomerular filtrationrate. Reduced fractional proximal tubular responsiveness toexogenous angiotensin II is consistent with a role for endogenousangiotensin II as one mediator of increased tubular reabsorptionof sodium in type I diabetes, but the data does not excludealternative mechanisms.     

Prognostic factors in acute renal failure due to sepsis. Results of a prospective multicentre study

BACKGROUND.: Sepsis is a major cause of acute renal failure in hospital patients,but its incidence and the associated prognostic factors haverarely been assessed prospectively by multivariate analysis. METHODS.: We conducted a prospective 6-month study in 20 multidisciplinaryintensive care units to assess the prognosis of patients hospitalizedwith acute renal failure due to sepsis. Sepsis syndrome andseptic shock were defined according to the criteria of the Societyof Critical Care Medicine Consensus Conference. Severity scoringindexes (SAPS, APACHE II, and organ system failure (OSF)) weremeasured on ICU admission and on inclusion. The end-point washospital mortality. RESULTS.: Acute renal failure had a septic origin in 157 patients (Group1), comprising 68 with septic shock and 89 with sepsis syndrome,and did not result from infection in 188 patients (Group 2).Patients with septic acute renal failure were older (mean age:62.2 versus 57.9 years, P<0.02) and had on inclusion a higherSAPS (19.3 versus 16.1, P<0.001), APACHE II (29.6 versus24.3, P<0.001), and OSF (2.07 versus 1.52, P<0.001) thanpatients with non-septic acute renal failure. They had a higherneed for mechanical ventilation (69.1% versus 47.3%, P<0.001),and acute renal failure was more often delayed during the ICUstay than was present on admission (47.7% versus 32.4% respectively,P<0.005). Hospital mortality was higher in patients withseptic acute renal failure (74.5%) than in those whose renalfailure did not result from sepsis (45.2%, P<0.001). Mortalitywas influenced by the presence of a septic shock (79.4%) orof a sepsis syndrome on inclusion (70.8%). Using a stepwiselogistic regression model, sepsis was an independent predictorof hospital mortality (OR, 2.51; 95% CI, 1.44–4.39) aswell as a delayed occurrence of acute renal failure, oliguria,an altered previous health status, hospitalization prior toICU, need for mechanical ventilation, age and severity scoringindexes on inclusion. In total patients, mortality was higherin dialyzed than in non-dialyzed patients (P<0.001), andin those treated by continuous compared to intermittent techniques(P<0.01). Patients dialysed with biocompatible membraneshad a lower mortality than those treated with cellulose membranes(P<0.005). CONCLUSIONS.: Patients with acute renal failure due to sepsis have a worseprognosis than those with non-septic acute renal failure. Sepsisand the above-defined predictive factors are to be consideredin studies on prognosis of ARF patients. Our results suggestthat the use of biocompatible membranes may reduce significantlymortality in these patients.     

Cyclosporin does not inhibit the tubular secretion of creatinine

BACKGROUND: The immunosuppressive drug cyclosporin is known to impair renalfunction. The degree of renal dysfunction is usually estimatedfrom the clearance of creatinine (C_Cr). Theoretically however,a fall in C_Cr can be caused by a decrease of GFR, an inhibitionof the tubular secretion of creatinine, or the combination ofboth. CsA has convincingly been shown to decrease GFR, but detailedinformation on the effects of CsA on tubular secretion of creatinineis lacking. METHODS: We performed two studies to investigate the influence of CsAon tubular creatinine secretion. In study A we simultaneouslymeasured C_Cr and GFR (using inulin) immediately before and 4weeks after cessation of CsA therapy in 17 renal transplantpatients. In study B, the rise in serum creatinine after administrationof cimetidine, which blocks the tubular secretion of creatinine,was compared in renal transplant patients treated with eitherCsA (in whom secretion might already be inhibited) or azathioprine. RESULTS: Study A: After cessation of CsA there was an increase of GFR(54±15 vs 63± 16 ml/min/1.73 m²; P>0.01) andof C_Cr (71±21 vs 82±23 ml/min/1.73 m²; P>0.01),but the ratio between C_Cr and GFR (a measure of the relativecontribution of tubular secretion to the clearance of creatinine)did not change significantly (1.33±0.21 vs 1.32±0.30).Study B: In nine couples of patients matched for GFR the relativerises in serum creatinine after administration of cimetidinewere 26±21% and 22±7% for the CsA and azathioprinetreated patients respectively (NS). CONCLUSIONS: CsA does not substantially inhibit the tubular secretion ofcreatinine. A rise in serum creatinine after administrationof CsA can thus be attributed completely to a fall in GFR.     

Relationship between donor renal interstitial surface and post-transplant function

Forty-three biopsies were performed between 30 and 60 min afterreperfusion. Patients (22 males/21 females, mean age 41 ±12years, mean donor age 32 ±14 years) were treated eitherwith antilymphocytic globulin, cyclosporin, and prednisolone(24 cases), or OKT3, cyclosporin, and prednisolone (19 cases).Ten patients had delayed post-transplant renal function (DPRF),defined as haemodialysis requirements after surgery, and sevenpatients had acute rejection 11 ±16 days post-transplant.Kidneys were perfused with a hypertonic solution containingmannitol. All patients were followed up for at least 30 months.During follow-up, five patients lost their grafts due chronicrejection, two patients due to non-compliance and one due torecurrence of focal seg-mental glomerulosclerosis. One patientdied from heart infarction. Biopsies were stained with H&E,Masson's trichrome, periodic acid-Schiff (PAS) and silver methenamine.Interstitial fibrosis, interstitial oedema, tubular vacuolization,and peritubular capillary oedema were measured using a semiquantitativescale. Five 400 x magnification micrographs of cortical inter-stitiumfrom silver-methenamine-stained sections were used to measurepercentage of interstitial surface with a morphometer. Interstitial surface was 18.7 ±6.2% (range 3.2–35.3%).A positive correlation was found between interstitial surfaceand donor age (r= 0.469, P=0.0015). No relationship was foundbetween warm and cold ischaemia times and tubular vacuolizationor peritubular capillary oedema. Patients with DPRF had a significantlyincreased interstitial surface (23 ±8%) when comparedwith patients without DPRF (17 ±5%), (P=0.014). Therewas a positive relationship between interstitial surface andnumber of days required to achieve a plasma creatinine of 300µmol/1 after surgery, this fitted an exponential curve(r=0.578, P=0.0012). Patients who had an episode of acute rejectionwere not included in this calculation. A positive correlationwas also found between interstitial surface and plasma creatinineat 12 months (r=0.692, P=0.0001), 18 months (r=0.713, P=0.0001),and 24 months (r=0.586, P=0.0023) after surgery. Patients wholost their grafts during follow-up were not included in thiscalculation. The relationship between interstitial surface andplasma creatinine 30 months after transplantation was not significant.There was no relation between tubular vacuolization or peritubularcapillary oedema and number of days required to achieve a plasmacreatinine of 300 µmol/1 or plasma creatinine 12, 18,24, and 30 months after transplantation. We conclude that assessment of donor renal biopsies may helpto predict post-transplant renal function. The increase of interstitialsurface due to pre-existing fibrosis is associated with poorpost-transplant graft performance.     

Relationship between hydrocarbon exposure and nephropathology in primary glomerulonephritis

It has been proposed that renal tubular damage and chronic hydrocarbonexposure are causally related to progression of renal failurein primary glomerulonephritis. We examined the relationshipbetween hydrocarbon exposure and morphological parameters oftubulointerstitial damage in 59 patients with biopsy-provenprimary glomerulonephritis (proliferative, n = 52; membranous,n = 7). From a mean follow-up period of 6 years patients weredivided into two groups (GP) according to the presence or absenceof progressive renal failure (GP 1, n = 24 with progressiverenal failure) and (GP 2, n = 35 without progressive renal failure).The two groups were comparable in age, sex, duration of diagnosis(since the time of biopsy) and blood-pressure control. Patientswere blindly assessed for chronic hydrocarbon exposure by avalidated questionnaire. Biopsy cylinders were blindly assessedretrospectively for relative interstitial volume of the renalcortex by the point-counting method. In addition an assessmentwas made of the degree of fibrosis and chronic inflammatorycellular infiltrate. Hydrocarbon exposure score derived from the questionnaire untilthe time of renal biopsy correlated both with interstitial volume(r=0.55; P<0.001) and serum creatinine (r=0.46; P<0.001).Moreover, interstitial volume also correlated with serum creatinine(r=0.63; P<0.001). Chronic hydrocarbon exposure scores andrelative interstitial volume in the renal cortex at the timeof renal biopsy was significantly higher in GP 1 than GP 2 (P<0.001). The degree of interstitial fibrosis and chronic inflammatorycellular infiltrate was also significantly higher in GP 1 thanGP 2 (P<0.01). At the time of renal biopsy patients fromGP 1 had a significantly higher mean serum creatinine than inGP 2 but the degree of proteinuria and proportion of patientswith hypertension were similar. The result of this study suggests that chronic hydrocarbon exposureand tubulointerstitial damage are causally interrelated andmay be important risk factors in the progression of renal failurein patients with primary glomerulonephritis. ^*Presently Postdoctorate Research Fellow, University of ColoradoHealth Sciences Center, CO, USA.     

Hypokalemic rhabdomyolysis in congenital tubular disorders: a case series and a systematic review

Hypokalemia is a recognized cause of rhabdomyolysis but very few reports document its association with inborn renal tubular disorders. We report our experience with hypokalemic rhabdomyolysis in 5 pediatric patients affected by inborn renal tubular disorders and the results of a careful review of the literature disclosing 9 further cases for a total of 14 patients (8 male and 6 female subjects, aged between 1.6 and 46, median 16 years). The inborn renal tubular disorders underlying rhabdomyolysis were classic distal renal tubular acidosis (n =?7), Gitelman syndrome (n?=?5), classic Bartter syndrome (n?=?1), and antenatal Bartter syndrome (n?=?1). In 8 patients rhabdomyolysis followed an acute intestinal disease, an upper respiratory illness or the discontinuation of regular medication. Five patients experienced two or more episodes of rhabdomyolysis. In 10 patients the underlying renal tubular disorder was recognized concurrently with the episode of rhabdomyolysis or some weeks later. In conclusion some congenital renal tubular disorders predispose to hypokalemic rhabdomyolysis. Prevention of discontinuation of regular medication and electrolyte repair in the context of acute intercurrent illnesses might avoid the development of hypokalemic rhabdomyolysis.     

Gene expression of plasminogen activator inhibitor 1 in transplant kidneys complicated by renal vein thrombosis: a combined study by in-situ hybridization and immunohistochemistry

In an attempt to understand the pathogenesis of renal vein thrombosisoccurring early after renal transplantation, gene expressionof plasminogen activator inhibitor-1 (PAI-1) was investigatedby an in-situ hybridization technique. The cases examined weresix transplant kidneys complicated by renal vein thrombosis,four ‘normal’ kidneys and five time-matched transplantkidneys not complicated by renal vein thrombosis but showingacute tubular necrosis, infection, or normal histology. Thecell types expressing PAI-1 mRNA were also studied by combinedin-situ hybridization and immunohistochemical double stainingtechniques. Our results showed that PAI-1 mRNA was expressedin transplant kidneys complicated by renal vein thrombosis butthere was no detectable expression in ‘normal’ kidneys,nor in time-matched transplant kidneys not complicated by thrombosis.Double staining showed that PAI-1 mRNA was predominantly expressedby capillary endothelial cells, particularly around large- ormedium-sized renal arteries and small nerves. Smooth-musclecells in the wall of major or medium-sized renal arteries alsoshowed positive expression of PAI-1 in three of six thrombosedtransplants. However, endothelium in the major renal vein showedrelatively little signal. The pattern was different from thatin rejection. The possible relevance of these findings is discussed.     

Proximal RTA: Are all the charts completed yet?

Renal tubular acidosis (RTA) is an uncommon disorder; however,the subgroup of isolated familial proximal RTA (pRTA) is exceedinglyrare. The term ‘isolated’ pRTA distinguishes thesedisorders from Fanconi syndrome, in which in addition to acidexcretion, other proximal tubular functions are impaired aswell. In this issue of Nephrology Dialysis Transplantation,Katzir et al. [1] report findings in a single family with aspecific form of isolated familial pRTA. It is highly likelythat only very few physicians will ever encounter a case ofthis nature in their professional lives. Why then would thisreport be of interest? The human body generates 50–100 mmol of     

肾综合征出血热病毒对肾小管上皮细胞损伤的研究

目的 研究肾综合征出血热病毒（ＨＦＲＳＶ）对肾小管上皮细胞（ＲＴＣ）的致病作用。方法 应用ＨＦＲＳＶ感染体外培养的人胚ＲＴＣ（ＨＦＲＴＣ）,采用原位分子杂交技术检测ＨＦＲＴＣ内的ＨＦＲＳＶ并作台盼蓝染色、透射电镜（ＴＥＭ）观察。结果 （１）ＨＦＲＳＶ能够直接感染培养的ＨＦＲＴＣ;（２）从第７天起被感染的ＨＦＲＴＣ死亡明显高于对照组;（３）ＴＥＭ观察表明ＨＦＲＳＶ可致ＨＦＲＴＣ的细胞膜、细胞器损害。