Acute renal failure secondary to oral ciprofloxacin therapy: a presentation of three cases and a review of the literature

The fluoroquinolones represent a new class of antimicrobial agents with a broad spectrum of activity. We report three cases of acute renal failure following ciprofloxacin in patients without a previous history of renal insufficiency. The average baseline creatinine was 1.1 mg/dl and rose to an average of 4.0 mg/dl during therapy. The length of antecedent ciprofloxacin therapy ranged from several days to several weeks. Other causes of acute renal failure and postobstructive uropathy were excluded. Kidney size was normal-to-increased. Gallium scans were positive in one of two patients studied. Peripheral eosinophilia developed in one case, suggesting an acute hypersensitivity reaction to the drug. The acute renal failure in all cases was non-oliguric and was completely reversed after discontinuation of ciprofloxacin. In two of the three reported cases there was an increased creatinine to BUN ratio, but increased production of creatinine (i.e., rhabdomyolysis) was unlikely with a normal serum creatinine phosphokinase (CPK). In addition, we performed in vitro studies which eliminated the possibility of methodological artifact. The nephrotoxicity of the quinolones has been linked to the development of crystalluria in experimental animals. However, in humans, crystalluria is unlikely and renal damage has not been noted. There have been only two previous case reports of acute renal failure due to oral ciprofloxacin therapy. In one, biopsy showed acute interstitial nephritis. We conclude that oral ciprofloxacin therapy may lead to acute renal failure secondary to tubulointerstitial nephritis characterized by an increased creatinine to BUN ratio. Patients placed on ciprofloxacin therapy need to be followed closely.     

Renal complications of drug addiction

The kidney is one of the target organs involved as a consequence of the systemic complications seen in drug abusers. This may manifest itself in one of the following forms: acute hepatitis with modest proteinuria (less than 2 Gm. per day); bacterial endocarditis with hematuria, azotemia, and a focal or diffuse glomerulonephritis; the nephrotic syndrome with focal mesangial sclerosis and diffuse interstitial nephritis often pursuing a fulminant course terminating in uremia; acute renal failure secondary to rhabdomyolysis and myoglobinuria; polyarteritis nodosa with renal involvement; and obstructive uropathy secondary to fungus ball in the urinary tract.     

Tubulointerstitial nephritis in the case of acute renal failure from sepsis after a cat bite]

Acute tubulointerstitial nephritis is associated with a variety of causes, such as drug interaction, and infectious or immunological mechanisms. We describe a patient who suffered from sepsis, septic shock, disseminated intravascular coagulation(DIC), hepatic failure and renal failure after receiving a bite from her house cat. The causes of her acute renal failure were initially thought to be due to circulatory failure with hypotensive shock, decrease in renal blood flow with fibrin formation by DIC, or microangiopathy such as hemolitic uremic syndrome. However, the renal biopsy on the 60th hospital day indicated tubulointerstitial nephritis, which was recognized by the presence of patchy and focal mononuclear small cell infiltration with invasion to the tubular epithelium. We concluded that prolonged renal failure was caused by tubulointerstitial nephritis. The cause of tubulointerstitial nephritis was not identified. Tubulointerstitial nephritis should be taken into consideration when the recovery from acute renal failure is slow.     

Drug-induced acute tubulointerstitial nephritis: a case with elevated urinary cadmium

Acute tubulointerstitial nephritis (ATIN) has many different causes, but is most frequently caused by drugs. We report a 13-year-old vegetarian girl with drug-induced ATIN, confirmed by renal biopsy, and simultaneous occurrence of elevated urinary cadmium. Four weeks prior to admission she had been treated with antibiotics and acetaminophen for respiratory infection, and remaining febrile, was treated with different ”home-made” herbal mixtures. She presented with acute non-oliguric renal failure, tubular dysfunction, and sterile pyuria, but without skin rash or edema. Laboratory data showed a raised erythrocyte sedimentation rate, normal white blood count with eosinophilia, and a serum creatinine of 245 μmol/l. Urinalysis was remarkable for glycosuria, tubular proteinuria, and elevated β₂-microglobulin and N-acetyl-beta-D-glucosaminidase excretion. Immunoserological tests characteristic of acute glomerulonephritis and systemic diseases were negative. She was treated with steroids and her renal function improved. Follow-up analyses disclosed normal urinary cadmium and enzyme excretion within 6 months. Heavy metal analysis of herbal preparations that she had taken confirmed the presence of cadmium, but within approved concentrations. In conclusion, elevated urinary cadmium in the case of drug-induced ATIN may be assumed to be an accidental finding. However, consumption of different herbs containing cadmium and cadmium-induced nephro-toxicity could be the reason for such serious renal damage. Received: 16 August 2001 / Revised: 11 January 2002 / Accepted: 13 January 2002     

Thyroidization in renal allografts

Abstract:  Thyroidization (thyroid-like appearance) in renal tissue which is made up of a colloid-like hyaline cast formation of Tamm-Horsfall glycoprotein (THP) is a common finding in chronic pyelonephritis and obstructive nephropathy. This type of pathological change is sometimes observed in renal allograft specimens. We examined allograft specimens for thyroidization and other pathological findings related to thyroidization to characterize the conditions causing such changes. One-hundred three patients who underwent renal transplantation between January 2006 and April 2008 at Gifu University Hospital (251 renal allograft biopsy specimens) were enrolled in this study. Sixteen patients had thyroidization (11 mild, 4 moderate, and 1 severe). In four patients, THP reflux on Bowman's capsule was found, and in three patients interstitial THP deposits were observed. In four patients, tubulointerstitial nephritis was diagnosed. Fifteen of 16 patients were examined for vesicoureteral reflux (VUR) with voiding cystourethrography. Three of 15 patients had VUR. In the past medical histories of the 16 patients with thyroidization, three had low capacity bladders, two had prostate diseases, and six had previous urinary tract infections. In cases of thyroidization with additional findings, including THP reflux into Bowman's space and interstitial THP deposits, we need to examine the patients for the presence of urinary tract diseases. In cases of thyroidization and tubulointerstitial nephritis urinary tract infections were suspected. Such subclinical urological diseases in the grafts might affect the prognosis of renal function. Therefore, appropriate management of urinary tract diseases is required.     

Acute renal failure in the course of HIV infection: a single-institution retrospective study of ninety-two patients anad sixty renal biopsies.

BACKGROUND: Acute renal failure syndromes are frequently encountered in patients with human immunodeficiency virus (HIV) infection. Most reported cases of acute renal failure are related to acute tubular necrosis, but many other causes of renal failure have been described in these patients. METHODS: The present work is a single-institution retrospective study of 92 HIV-infected patients with acute or rapidly progressing renal failure. In 60 cases, a renal biopsy was performed. For each patient we analysed clinical and pathological data, as well as the short-term prognosis. RESULTS: Ten different causes of acute or rapidly progressing renal failure were documented: (i) haemolytic uraemic syndrome (32 patients); (ii) acute tubular necrosis either of ischaemic-toxic origin (18 patients) or due to rhabdomyolysis (six patients); (iii) obstructive renal failure which was either extrinsic (two patients), drug-induced (13 patients) or secondary to paraprotein precipitation (one patient); (iv) HIV-associated nephropathy (14 patients); (v) acute interstitial nephritis (two patients); (vi) various glomerulonephritis (four patients). In most cases, renal failure was severe (the mean creatinine clearance at entry was 12 ml/min). Most patients had a significant improvement in renal function with only symptomatic treatment. Eighteen per cent of the patients died within 2 months of the diagnosis of renal failure. Renal biopsy seems important for the diagnosis but also for the prognosis, at least in the cases of haemolytic-uraemic syndrome, HIV-associated nephropathy and drug-induced micro-obstructive renal failure. CONCLUSION: Vascular and glomerular diseases are frequent causes of acute or rapidly progressing renal failure in HIV-infected patients. Renal biopsy appears to be safe and useful for the diagnosis and the prognosis of the renal failure. High mortality rate is only observed in patients with ischaemic/toxic causes of acute renal failure.     

Indinavir-associated tubulointerstitial renal disease

Indinavir, used for the treatment of HIV disease, forms distinctive crystals in the urine. The crystalluria has been associated principally with several urinary tract abnormalities which may require discontinuation of the drug. We present a case of progressive leucocyturia and renal impairment occurring during indinavir treatment which illustrates vividly the impact of the crystalluria on the tubulointerstitial renal compartment.     

Nondilated obstructive uropathy

Four patients presented with severe renal failure secondary to urinary tract obstruction, yet ultrasonography and/or computed tomography revealed only minimal dilatation in 1 patient and no dilatation in the other three. Two patients had prostate cancer, one had bladder cancer, and one had retroperitoneal fibrosis. In all cases, relief of obstruction led to a dramatic improvement in renal function. These cases, and others in the literature, illustrate that in certain settings severe urinary tract obstruction may be present in the absence of dilatation and hence may be missed by noninvasive imaging techniques. Nondilated obstructive uropathy should be suspected in any elderly patient who presents with the acute onset of oliguria in the absence of an identifiable cause, especially if there is a previous history of malignancy in the pelvis. Left undiagnosed, this potentially reversible cause of renal failure can lead to end-stage renal disease.     

Donor calculi induced acute renal failure

Nephrolithiasis is an infrequent complication following renal transplantation and acquisition of a stone with the donor kidney is rare. Indeed only a few cases of donor stones causing renal failure have been reported. Since the grafted kidney is denervated, stone disease may not present with the classic renal colic but rather with acute renal failure secondary to the obstruction. Identification of the precise cause is critical in order to avoid inappropriate therapy. We present our experience of two renal transplant patients who developed obstructive uropathy by stones originating from the donor kidneys.     

Potential nephrotoxicity of intravenous infusions of naftidrofuryl oxalate

We report two cases of acute renal failure in patients witharteriosclerosis obliterans treated by intravenous infusionof naftidrofuryl oxalate. At renal biopsy the histological lesionswere identical with those found in ARF due to hyperoxaluriaof other causes, revealing tubular epithelial necrosis and massiveintra-tubular precipitation of calcium oxalate monohydrate (Cl)crystals. A second study was then conducted in four other patientswith arteriosclerosis obliterans to evaluate serum and urinarylevels of oxalate, and crystalluria during the intravenous administrationof 800 mg of naftidrofuryl oxalate per day for 10 days. Duringthe course of treatment, the serum and urinary oxalate levelswere found to increase substantially, with the gradual onsetof massive Cl crystalluria. These results indicate that naftidrofuryloxalate was responsible for the acute renal failure in the firsttwo patients. High intravenous doses of naftidrofuryl oxalatemust be used cautiously, with close surveillance of renal function.     

A case of idiopathic chronic interstitial nephritis progressed to renal failure without proteinuria nor hematuria]

A case of idiopathic interstitial nephritis who underwent to chronic renal failure without history of hematuria nor proteinuria is discussed. A 46 years old woman who showed gradually elevation of serum creatinine (1.3-2.5 mg/dl) admitted on our hospital. On occasions of pregnancy, health examination or hospital visit, she has never been pointed out hematuria nor proteinuria. Immunological disorders such as SLE, metabolic diseases, urinary tract obstruction and chronic urinary tract infection were excluded by the examinations after admission. Because of the severe enzymuria (beta 2-microglobulin, N-acetyl glucosaminidase), chronic interstitial nephritis was considered, and renal biopsy was performed. Severe tubulointerstitial changes were observed histologically, however, glomerular damage was comparatively mild. From these results, she was diagnosed idiopathic chronic tubulointerstitial nephritis. In this case, hematuria and proteinuria were absent until severe renal dysfunction. This may be caused by that inflammation was located to the tubulointerstitial area. The observation of enzymuria seemed to be important to diagnosis and follow-up of the interstitial nephritis.     

Drug-induced granulomatous interstitial nephritis in a pediatric patient

Acute interstitial nephritis (AIN) is a known cause of acute renal failure in children. In most instances, drug therapy is the offending agent. Although granuloma formation has been observed in drug-induced interstitial nephritis, it is not a commonly associated manifestation. This is a case of a 15-year-old white female with Tetralogy of Fallot and pulmonary atresia who developed acute renal failure secondary to drug-induced interstitial nephritis and renal granulomas. In addition to interstitial edema with eosinophils and lymphocytes, her renal biopsy showed interstitial granulomas, immune complexes within tubular basement membranes, and the unusual feature of multinucleated giant cells engulfing tubules. Her acute renal failure resolved after the withdrawal of antibiotics and the initiation of intravenous steroid therapy.     

Slightly dilated acute obstructive failure of congenital solitary kidney

We present a case of a 10-year-old boy with slightly dilated obstructive acute failure of congenital solitary kidney. Obstruction of the ureter by stone was suggested as a cause of renal failure. The dilatation of the urinary tract above the obstruction was very small.     

Bilateral hydroureter and hydronephrosis causing renal failure due to a procidentia uteri: a case report

We report a case of complete uterine prolapse that resulted in bilateral hydroureter, hydronephrosis, and renal dysfunction. The nonoperative reduction of the prolapse with a vaginal pessary reversed the obstructive uropathy and ameliorated renal function. The lower urinary tract should be imaged in patients with complete uterine prolapse. If present, obstructive uropathy should be relieved by the reduction of the prolapse before irreversible renal damage occurs.     

Tubulointerstitial changes in systemic vasculitic disorders: a quantitative study of 18 biopsy cases

Tubulointerstitial alterations were studied in 18 biopsy cases of systemic vasculitis. To evaluate the changes more objectively, two indexes, the number of interstitial inflammatory cells and tubulitis percentage, were used. The group means of both of these indexes were statistically higher than those of the autopsy control group, while 14 of the cases (77.8%) showed a significant difference (P less than 0.01) between individual means and the control group means. On the other hand, tubulointerstitial changes in systemic vasculitis seemed to be less prominent than drug-induced tubulointerstitial nephritis (TIN) according to these indexes. However, comparing these indexes with those of drug-induced TIN, six cases (33.3%) of systemic angiitis could be regarded as having developed pathologic changes similar to TIN. Statistical difference was not shown in the indexes between those patients with histologic evidence of necrotizing angiitis and those without it. Clinically, urinary N-acetyl-beta-D-glucosaminidase (NAG) was abnormally high in all three examined cases, reflecting the damage of renal tubular epithelial cells. Not only the vascular and glomerular lesions, but also tubulointerstitial changes, should be evaluated in the renal biopsy specimen of systemic vasculitis.     

Tubulointerstitial nephritis

Tubulointerstitial nephritis (TIN) describes a range of pathological processes that are at least partly responsible for the progression of renal disease of nearly all aetiologies. TIN is frequently the most important pathological manifestation of progressive glomerulonephritis, obstructive uropathy, reflux nephropathy and cystic diseases, although it may also present as a primary disease process associated with infection, drug use or other immunologically mediated disease. Recent clinical and laboratory research has increased our knowledge of tubulointerstitial structure, physiological function and tubulointerstitial response to injury. This review presents a classification of TIN in which acute and chronic tubulointerstitial diseases are recognized as forming a continuum. Primary TIN and TIN associated with glomerulonephritis, obstructive nephropathy and chronic progressive renal disease are discussed from both clinical and pathogenic aspects. It is argued that chronic TIN is a disease process in which inflammation is accompanied by a destructive tubulopathy and fibrogenesis. In acute TIN there is a cessation and reversal of this process. It is suggested that most forms of TIN have an immunological basis because of the presence of immune cell infiltrates, the occurrence of TIN in several immune diseases and immunological animal models of TIN. However, to date TIN has not been convincingly modified in patients by immune manipulation. Experimental evidence suggesting an important pathogenic role for proteinuria and antigenuria, and the renal tubule cell acting as an antigen-presenting cell is discussed.     

Emergency percutaneous nephrostomy in the septic kidney.

From 250 upper tract obstructive uropathy cases we have studied 64 patients hospitalized with toxico-septic shock. The constant symptom was arterial hypotension. Other 3 patients with long-standing urinary infection due to lithiasis developed this dreaded complication after PNL (staghorn stones-2, pyelic stone-1). In complicated obstructive uropathy cases associated with toxico-septic shock, percutaneous nephrostomy for high urinary derivation in emergency is usually made under local anaesthesia. Its aim is rapid and efficient clearance of kidney obstruction, with minimal damage for the patient; then it is followed by strong antibiotherapy associated with other reanimation and intensive care measures. There were 11 deaths. The stone generating obstructive uropathy was removed subsequently, after the improvement of biological constants and general state of the patient, under the protection of percutaneous nephrostomy.     

HLA-DR display by renal tubular epithelium and phenotype of infiltrate in interstitial nephritis

Renal tubular display of HLA-DR was estimated semi-quantitatively in 28 biopsies from 27 patients with various forms of tubulointerstitial nephritis (10 following use of non-steroidal anti-inflammatory drugs) using a monoclonal anti-MHC class II non-polymorphic antibody (DK-22). Normal donor kidneys and biopsies from patients with minimal-change nephrotic syndrome were examined as controls. The phenotype of infiltrating cells was also studied quantitatively, using monoclonal antibodies on frozen biopsy tissue; the number of cells infiltrating the interstitium was counted per tubular cross-section. Display of HLA-DR was seen in up to 5% of control tubular cells, but up to 100% expressed HLA-DR in tubulointerstitial nephritis biopsies. There was a correlation between the expression of HLA-DR and the severity of both tubular atrophy and tubulointerstitial fibrosis judged semi-quantitatively by optical microscopy. In controls up to 50 leucocytes per tubular cross-section were evident, but in patients with tubulointerstitial nephritis up to 1500 were observed, approximately 50% being T-lymphocytes, the majority expressing the helper phenotype except in early, active drug-induced tubulointerstitial nephritis; the remainder were mostly monocytes. There were no qualitative differences between the different causes of tubulointerstitial nephritis. Tubular DR expression correlated with the number of DR-positive cells in the interstitium, but not with total leucocytes or T-lymphocytes. HLA-DR tubular expression was greater in the early stages than late stages of NSAID-induced tubulointerstitial nephritis, but this relationship was not present in the group as whole. HLA-DR expression by renal tubular epithelial cells may play a role in localising or amplifying tubular injury in tubulointerstitial nephritis.     

上尿路结石致急性梗阻性肾功能不全的诊疗体会

目的：探讨上尿路结石致急性梗阻性肾功能不全的诊断和治疗手段的选择以及预后。方法：回顾性分析2004年1月～2008年10月收治的57例上尿路结石致急性梗阻性肾功能不全患者的临床资料，分别通过膀胱镜逆行插管、输尿管镜碎石、开放取石、血液透析等方法处理。结果：57例患者经相关处理后均获得一定疗效．肾功能均较前有所改善。其中27例肾功能完全恢复正常，23例肾功能处于代偿期，5例处于失代偿期．1例处于衰竭期，1例需永久透析。结论：对于上尿路结石致急性梗阻性肾功能不全患者，应尽快明确诊断，严格把握治疗原则，选择适当的治疗方法，可以获得良好的疗效。     

Development of renal function after neonatal urinary ascites due to obstructive uropathy

PURPOSE: Neonatal urinary ascites is a rare complication of obstructive uropathy with possible lethal outcome if not treated adequately. We demonstrate that with adequate therapy the survival rate can be high and long-term survival, kidney function and lower urinary tract function of patients with urinary ascites can be good. MATERIALS AND METHODS: The study included 4 females and 8 males born with urinary ascites. Followup ranged from 3 to 14 years. Blood analysis for renal function, electrolytes and blood gas was performed at hospitalization and during followup. Ultrasound, cystourethrograms or cystoscopy showed the site of obstruction and leakage of urine. All patients were initially treated with drainage of the ascites and decompression of the obstructed urinary tract. All patients underwent surgery to remove the obstruction and reconstruct the urinary tract. Bladder and kidney function was evaluated at long-term followup. RESULTS: All patients had severe abdominal distention at presentation. Severe metabolic acidosis was present in cases that had not been detected prenatally or immediately after birth. Two patients died of causes related to pulmonary hypoplasia. Surprisingly urinary continence and renal function were good in 9 of 10 survivors. CONCLUSIONS: Long-term outcome of bladder and kidney function is surprisingly good in cases of severe obstructive uropathy with ascites. Intrauterine pressure relief of the bladder through urinary extravasation protects renal function and this decompression of the urinary tract prevents severe secondary changes to bladder function. Although not proven we believe that high intrauterine pressures in the abdominal cavity are prevented by peritoneal absorption of the extravasated urine and consequent dialysis through the placenta.