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Purpose: The aim of the study was to analyze the occurrence of primary and secondary glomerulopathies as well as tubulointerstitial nephropathies over time and to assess potential changes in the disease spectrum., Patients and Methods: The authors retrospectively analyzed all kidney biopsies performed in their institution between 1983 and 2006 as well as the clinical data at the time of biopsy., Results: Between January 1983 and December 2006, 359 native kidney biopsies with sufficient material for histological analysis were performed (218 men, 141 women; mean age 51.8 years). A mean of nine glomeruli per biopsy were obtained. Mean serum creatinine at the time of biopsy was 3.3 mg/dl. The most common indication for biopsy was nephrotic syndrome (31%), followed by renal insufficiency (29%) and proteinuria (14%). Primary glomerulopathies were found in 51%, secondary glomerulopathies in 28%, tubulointerstitial renal diseases in 9%, and vascular renal diseases in 12%. Among the primary glomerulopathies, IgA nephropathy was the most common diagnosis (26%), followed by mesangioproliferative glomerulonephritis (17%), membranous glomerulonephritis (16%), minimal change disease (14%), focal segmental glomerulosclerosis (FSGS; 13%), rapidly progressive glomerulonephritis (RPGN; 8%), and membranoproliferative glomerulonephritis (7%). Among the secondary glomerulopathies, the heterogeneous group of autoimmune diseases (26%) and diabetic nephropathy (25%) dominated. Comparing the period from 1983 to 1994 with 1995 to 2006, a decrease in primary FSGS from 16% to 9% as well as in RPGN from 14% to 1% was noticed, while among the secondary forms, autoimmune diseases with renal involvement increased from 14% to 31%., Conclusion: In the own patient population changes in the spectrum of primary and secondary glomerulopathies can be observed over time. Thereby, the distribution pattern of the various glomerulonephritides largely corresponds to the distribution described for other West European countries. An increase in the incidence of primary FSGS, as observed in non-European countries, could not be demonstrated.

During the last decade, the human polyomaviruses (BK virus and, much less commonly, JC virus) have entered the realm of routine clinical decision making for providers caring for kidney transplant recipients. The emergence of polyomavirus-associated nephropathy (PVAN) as an important clinical entity coincided with the development and use of more potent immunosuppression agents, currently the only clear risk factor for reactivation of the virus. Ongoing efforts to define the pathogenesis, clinical presentation, and appropriate management of PVAN have led to a greater ability to prevent and control viral-induced interstitial nephritis despite continued deficiencies in our understanding of risk factors for disease and lack of published prospective polyomavirus-specific antiviral trials. The purpose of this review is to summarize advances made during the last decade and highlight emerging data that address common clinical considerations the clinician currently faces in the understanding and management of PVAN.

We report a 43-year-old woman with tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) presented with a 5-day complaint of chills and fever, anorexia, nausea, and vomiting. She had elevated BUN and creatinine and urinalysis revealed decreased concentration, proteinuria, hematuria, and pyuria. A kidney biopsy showed non-caseating granulomatous tubulointerstitial nephritis. She suffered from anterior uveitis one month before, which was managed with local ophthalmic steroids. She received two months of oral high dose prednisolone, which was tapered over the next two months, and two months of 2 mg/kg cyclophosphamide. Her renal function recovered during the first two months. Her kidney and ocular symptoms did not recur during one year of follow-up. We suggest short course of cyclophosphamide and prednisolone for treatment of TINU syndrome to decrease the recurrence of kidney and ocular involvement.

Regardless of etiology, all patients with chronic renal disease show a progressive decline in renal function with time. Fibrosis, so-called scarring, is a key cause of this pathophysiology. Fibrosis involves an excess accumulation of extracellular matrix (primarily composed of collagen) and usually results in loss of function when normal tissue is replaced with scar tissue. While recent major advances have led to a much better understanding of this process, many problems remain. We for instance know little about why some wounds heal and others scar and little about how many putative antifibrotic agents work. This review discusses recent advances in our understanding of the mechanisms of tubulointerstitial fibrosis, focusing on the regulation and role of the myofibroblast in this process, the role of recently recognized endogenous antifibrotic factors, controversy surrounding the effects of metalloproteinases, and the opportunities presented by new treatment strategies that abrogate and may even reverse fibrosis.

Aristolochic acid nephropathy (AAN), a progressive renal interstitial fibrosis frequently associated with urothelial malignancies, was initially reported in a Belgian cohort of more than 100 patients after the intake of slimming pills containing a Chinese herb, Aristolochia fangchi. Although botanicals known or suspected to contain aristolochic acid (AA) were no longer permitted in many countries, several AAN cases were regularly observed all around the world. The incidence of AAN is probably much higher than initially thought, especially in Asia and the Balkans. In Asian countries, where traditional medicines are very popular, the complexity of the pharmacopoeia represents a high risk for AAN because of the frequent substitution of the botanical products by AA-containing herbs. In the Balkan regions, the exposure to AA found in flour obtained from wheat contaminated with seeds of Aristolochia clematitis could be responsible for the so-called Balkan-endemic nephropathy. Finally, despite the Food and Drug Administration's warnings concerning the safety of botanical remedies containing AA, these herbs are still sold via the Internet.

Background: Documentation regarding the renal complications of paediatric HIV infection from developing countries is scarce. In the era prior to highly active antiretroviral therapy (HAART), HIV-infected children in Jamaica who developed HIV-associated nephropathy (HIVAN) progressed to end stage renal disease (ESRD) and death within a few months of diagnosis. With increased public access to antiretroviral therapy since 2002 and subsequent survival, renal complications are increasingly recognized among the surviving cohort of infected children., Methods: A cohort of 196 HIV-infected children was followed in four multicentre ambulatory clinics from September 1, 2002 to August 31, 2005 as part of the Kingston Paediatric and Perinatal HIV/AIDS Programme, Jamaica. We describe the clinical presentations and natural history of those patients who developed renal complications., Results: Urinary tract infections were the most common diagnosis, occurring in 16.8% of patients, with a high recurrence rate and the most common organism was Escherichia coli. Four of seven patients who started indinavir developed complications of nephrolithiasis and tubulointerstitial nephropathy. Six patients (3%) fulfilled the criteria for HIVAN, five of whom were male. Median age at diagnosis was five years; all presented with advanced HIV disease, nephrotic syndrome or nephrotic range proteinuria and three with chronic renal failure. Patients received standard medical management and were initiated on angiotensin-converting enzyme (ACE) inhibitors and HAART While the mortality ratio was 50%, only one death was associated with HIVAN and the median survival time was 3.1 years., Conclusions: HIV-infected children present with a variety of renal complications. With improved survival since the introduction of HAART, the incidence of HIVAN is expected to increase among this maturing paediatric cohort. Early detection and treatment will optimize the outcomes for these children.

Background and Objectives: Renal biopsy in acute renal failure of unknown origin provides irreplaceable information for diagnosis, treatment, and prognosis. This study analyzed the frequency and clinicopathologic correlations of renal native biopsied acute renal failure in Spain during the period 1994 through 2006., Design, Setting, Participants, & Measurements: Acute renal failure was defined as a rapid deterioration of glomerular filtration rate, with or without oligoanuria or rapidly progressive renal insufficiency, including acute-on-chronic renal failure. Patients who were younger than 15 yr were considered children, those between 15 and 65 yr adults, and those >65 elderly., Results: Between 1994 and 2006, data on 14,190 native renal biopsies were collected from 112 renal units in Spain. Of these, 16.1% (2281 biopsies) were diagnosed with acute renal failure. The prevalence of the main clinical syndromes was different in the three age groups: Biopsy-confirmed acute renal failure in children was 5.7%, in adults was 12.5%, and in elderly increased significantly to 32.9%. The prevalence of biopsy-confirmed acute renal failure according to cause was as follows: Vasculitis, 23.3%; acute tubulointerstitial nephritis, 11.3%; and crescentic glomerulonephritis types 1 and 2, 10.1%. The prevalence of the different causes differed significantly according to age group., Conclusions: The Spanish Registry of Glomerulonephritis provides useful information about renal histopathology in biopsy-confirmed acute renal failure. The prevalence of vasculitis and crescentic glomerulonephritis is high, especially in elderly patients. These data obtained from a national large registry highlight the value of renal biopsy in undetermined acute renal failure.

Antiretroviral therapy (ART) has made a significant impact on the morbidity and mortality of patients with HIV infection. However, many of these agents have nephrotoxic potential and are implicated in causing both acute and chronic kidney disease. Safely employing these medications requires a thorough understanding of risk factors that predispose to kidney injury, which include both patient-related characteristics as well drug-related factors. Acute tubular toxicity, crystal nephropathy, and acute interstitial nephritis are among the common renal manifestations of these drugs. Adefovir and tenofovir are associated with tubular toxicity. Crystalluria, crystal nephropathy and nephrolithiasis have been established with indinavir. Acute interstitial nephritis, although not common among antiretroviral agents, is seen with indinavir and atazanavir in these immunocompromised patients. Rarely, enfuvirtide may promote a glomerulopathy. Frequent exposure to other nephrotoxic non-antiretroviral drugs also contributes to kidney disease. Identification and reversal of potentially modifiable risk factors prior to drug administration is important to limiting kidney injury. Recognition of drug-related nephrotoxicity will promote earlier resolution of acute kidney injury and reduce the development of chronic kidney disease.

Background: Tubulointerstitial nephritis and uveitis (TINU) syndrome is characterized by a combination of idiopathic acute tubulointerstitial nephritis and uveitis. Krebs von den Lunge-6 (KL-6) is a human glycoprotein secreted by type II alveolar cells in the lung, and its serum levels increase in patients with pneumonia of various causes, as well as ocular sarcoidosis. The aim of the present study is to quantify serum KL-6 levels in patients with TINU syndrome, which has no pulmonary and sarcoid lesions, and elucidate the usefulness of KL-6 for the diagnosis and follow-up of this syndrome., Methods: Serum and urinary samples were obtained from 17 patients with TINU syndrome and 36 age-matched patients with uveitis from other causes. Sarcoidosis was eliminated because serum KL-6 levels increased during their lung lesion. Serum KL-6 level was determined by using a human KL-6 electrochemiluminescence immunoassay. Formalin-fixed paraffin-embedded renal tissue sections were incubated with anti-KL-6 monoclonal antibody, then examined immunohistochemically., Results: Mean serum KL-6 levels for patients with TINU syndrome and those with uveitis from other causes were 363.35 +/- 51.06 and 213.19 +/- 10.28 U/mL, respectively (P < 0.001). Urinary beta(2)-microglobulin levels of patients with TINU syndrome and uveitis from other causes were 4.06 +/- 1.31 and 0.16 +/- 0.20 mg/L, respectively (P < 0.001). All patients with TINU syndrome showed a simultaneous decrease in serum KL-6 and urinary beta(2)-microglobulin levels after the beginning of treatment. Strong immunoreactivity for KL-6 was observed in renal distal tubules in biopsy tissue of patients with TINU syndrome., Conclusion: We show a significant increase in serum KL-6 levels in patients with TINU syndrome, whereas levels were normal in patients with other causes of uveitis without nephritis. Renal distal tubules stained strongly with anti-KL-6 antibody, suggesting that high KL-6 levels may reflect the renal lesion of TINU syndrome. Serum KL-6 may be a potential laboratory parameter for the diagnosis and follow-up of patients with TINU syndrome that could complement urinary beta(2)-microglobulin measurements.

Aim: Although proton pump inhibitors (PPI) are usually safe and effective therapeutic agents, serious adverse effects can occur. The aim of the present study was to report and analyse the clinical features of 15 patients with acute interstitial nephritis (AIN) and acute renal failure from PPI that were referred to renal services in Auckland over a period of 3 years., Methods: The clinical presentation, therapeutic drugs, demographic details and renal outcome of the patients were considered. The population at risk and total PPI exposure were able to be defined. The diagnosis of AIN was made by renal biopsy in 12 cases. In all patients, the time-course of drug exposure and improvement of renal function on withdrawal suggested PPI were causal., Results: The median patient age was 78 years. The mean baseline serum creatinine level was 83 micromol/L, peak level 392 micromol/L, and recovery level 139 micromol/L. The erythrocyte sedimentation rate (ESR) and C-reactive protein were elevated at the time of diagnosis in the 11 and 12 patients, respectively, where this information was collected (ESR mean 85 mm/h, and C-reactive protein mean 81 mg/L). AIN occurred at 8 per 100 000 patient years (95% confidence level 2.6-18.7 per 100 000 patient years). Although four patients presented with an acute systemic allergic reaction, 11 were asymptomatic with an insidious development of renal failure., Conclusion: PPI are now the most commonly identified cause of AIN in the Auckland area. Recovery occurs after withdrawal of the drug but is often incomplete. Early diagnosis may be facilitated by clinician awareness of the insidious onset of renal failure, and an elevated erythrocyte sedimentation rate and C-reactive protein.

Background: The present study explores the influence of psychosocial adversities on the etiology and progress of interstitial cystitis (IC)., Methods: A systematic survey of the childhood risk factors was carried out using a specially developed, structured interview for pain patients (MSBA-Mainzer Strukturierte Biographische Anamnese) and additionally the Brief Symptom Inventory (BSI). Essentially a descriptive evaluation was performed. Thirty IC patients who fulfilled the current diagnostic criteria participated in the study., Results: The investigation showed higher values for relevant childhood adversities in IC patients. A poor emotional relationship with both parents, chronic diseases of the parents, and physical maltreatment were frequently reported. In the cumulative adverse childhood experience score IC patients showed higher levels than published data of healthy control groups. The contemporary social history did not show relevant psychosocial adversities. The quality of life is extremely reduced because of IC symptoms. The BSI showed high levels especially in the dimensions somatization, anxiety, and phobic anxiety., Conclusion: The results of this study argue for a participatory role of psychosomatic factors in the assumed multifactorial etiology of interstitial cystitis.

Context: Thin glomerular basement membrane (GBM) nephropathy is often equated with benign familial hematuria, although it may occur sporadically and may not always be benign. Thin GBM nephropathy is reported to occur in at least 1% of the population, although its reported incidence varies considerably in different studies because there are presently no uniform criteria for its diagnosis by electron microscopy (EM)., Objective: To determine the incidence of thin GBM nephropathy in a large sample of renal biopsies using a basic methodology that can easily be applied in any diagnostic EM laboratory., Design: Direct measurements of GBM thickness were made from electron micrographs at 3 specified points along each of 10 randomly selected glomerular capillaries to determine an average GBM thickness for each of 50 males and 50 females, ages 9 to 80 years, with minimal-change nephropathy or acute interstitial nephritis, without hematuria. The means of the average GBM thickness values were 330 +/- 50 (SD) nm in the males and 305 +/- 45 nm in the females; normal ranges for each sex were defined as being within 2 SD of these means. The average GBM thickness was then similarly determined for renal biopsies with suspected thin GBMs examined from January 2000 to December 2004; a total of 3471 renal biopsies were examined by EM during this period., Setting: Academic medical center renal pathology/EM laboratory., Results: Excluding biopsies with immunoglobulin A nephropathy, which is known to be frequently associated with thin GBMs, and biopsies with Alport syndrome, 67 biopsies (1.9% of total) had an average GBM thickness below the sex-specific normal range. Of these, 37 biopsies were performed specifically because of hematuria and had an average GBM thickness of 121 to 215 nm (mean, 185 +/- 20 nm). The remaining 30 (0.9%) biopsies, with average GBM thicknesses of 143 to 227 nm (mean, 190 +/- 20 nm), represent cases of incidentally discovered thin GBM nephropathy., Conclusions: Based on the frequency of incidentally discovered cases and taking into account excluded cases and biopsies (eg, with diabetic nephropathy) in which diagnosis of incidental thin GBM nephropathy by EM is not possible, the incidence of thin GBM nephropathy in our population is estimated to be between 1% and 2%. Diseases most often associated with incidental thin GBM nephropathy were focal segmental glomerulosclerosis (10 cases) and minimal-change nephropathy (5 cases).

Background & Aims: Proton pump inhibitors (PPIs) are a widely prescribed class of drugs, and their usage worldwide is increasing. Although well-tolerated, there have been case reports and a recent case series implicating these drugs in acute interstitial nephritis (AIN) and progression to acute renal failure (ARF). The aim of this study was to investigate how widespread this complication is in Australia, to identify which PPIs are implicated, and to establish whether PPI-induced AIN is a class effect., Methods: We undertook a retrospective case review of potential cases at 2 teaching hospitals and a review of registry data from the Therapeutic Goods Administration of Australia (TGA). Parameters sought included the drug implicated, concurrent medications, symptoms, signs, serum creatinine, and time of onset after prescription., Results: We identified 18 cases of biopsy-proven PPI-induced AIN causing ARF in the retrospective case review, which is the largest hospital-based case series to date. The TGA registry data identified an additional 31 cases of "biopsy proven interstitial nephritis." An additional 10 cases of "suspected interstitial nephritis," 20 cases of "unclassified acute renal failure," and 26 cases of "renal impairment" were also identified. All 5 commercially available PPIs were implicated in these cases., Conclusion: With the ever more widespread use of this class of medications, PPI-induced AIN is likely to become more frequent. There is now evidence to incriminate all the commercially available PPIs, suggesting there is a class effect. Failure to recognize this entity might have catastrophic long-term consequences including chronic kidney disease. Increased awareness might facilitate more rapid diagnosis and management of this potentially reversible condition.

As a cause of graft dysfunction, tubulointerstitial nephritis (TIN) seems to be the third most common pathology after rejection and cyclosporine nephrotoxicity. Among 540 needle biopsies obtained from 280 renal transplant patients between 1996 and 1999, acute TIN was detected in 23 patients (8%). The cause of acute TIN was secondary to bacterial infection in 17 patients and secondary to cytomegalovirus (CMV) infection in three patients. The remaining three cases showed granulomatous pyelonephritis due to Mycobacterium tuberculosis (n = 2) and Candida albicans (n = 1). During follow-up, 13 of 23 patients (56.5%) showed at least one acute rejection episode. The average number of urinary tract infection (UTI) episodes in the 23 patients was 1.4 +/- 07. We observed that the number of UTI episodes showed a significant association with the development of chronic allograft nephropathy (P = .03) and graft loss (P < .01). Twelve patients (52.2%) lost their grafts during 5 years posttransplantation. Only 6 of 17 patients with bacterial TIN lost their graft at a mean time of 52.5 +/- 14 months. But all patients with CMV TIN or granulomatous TIN lost their grafts at a mean time of 31 +/- 3.1 months and 39 +/- 3 months, respectively (P < .05). In conclusion, these results support the pathological role of tubulointerstitial nephritis as a pathway of graft rejection or renal allograft deterioration among recipients after transplantation.

Primary biliary cirrhosis (PBC) is characterized by high frequency of systemic extrahepatic manifestations (EHM), which often precede the development of full clinical picture of PBC and play the leading part in the clinical course of the disease, sometimes determining its prognosis. The examination of 145 PBC patients (including two men) found a frequency of EHM of 72. 4%. The majority of EHM were caused by delayed-type hypersensitivity reactions, such as Sjogren syndrome, fibrosing alveolitis, autoimmune thyroiditis, tubulointerstitial nephritis, pulmonary granulomatosis/sarcoidosis, systemic scleroderma, rheumatoid arthritis, and ulcerative colitis; immunocomplex pathology including vasculites involving blood vessels of different caliber and localization and polyneuropathy was rarer. In 24.1% of PBC patients, system EHM manifestations were the first clinical signs of the disease. In 62.8% of patients with EHM their different combinations were registered. The most frequent one was a combination of Sjogren syndrome, fibrosing alveolitis, and tubulointerstitial nephritis, which was found in 16.2% of the patients. 6 7% of the patients had a combination of four EHM - Sjogren syndrome, fibrosing alveolitis, tubulointerstitial nephritis, and autoimmune thyroiditis. A long duration of PBC (more than five years from the debut), stage IV of the disease, and the presence of the rheumatoid factor in blood serum, were risk factors of the development of system PBC manifestations. In 20% of EHM patients their symptoms prevailed in the clinical picture, thus determining the severity of the condition. Three patients died of system EHM of PBC (systemic scleroderma, pulmonary granulomatosis). Thus, PBC diagnostics must be performed with taking into account system EHM found in this category of patients.

Apolipoprotein A-I amyloidosis is a rare, late-onset, autosomal dominant condition characterized by systemic deposition of amyloid in tissues, the major clinical problems being related to renal, hepatic, and cardiac involvement. Described is the clinical and histologic picture of renal involvement as a result of apolipoprotein A-I amyloidosis in five families of Italian ancestry. In all of the affected family members, the disease was caused by the Leu75Pro heterozygous mutation in exon 4 of apolipoprotein A-I gene, as demonstrated by direct sequencing and RFLP analysis. Immunohistochemistry confirmed that amyloid deposits were specifically stained with an anti-apolipoprotein A-I antibody. The clinical phenotype was mainly characterized by a variable combination of kidney and liver disturbance. The occurrence of renal involvement seemed to be almost universal, although its severity varied greatly ranging from subclinical organ damage to overt, slowly progressive renal dysfunction. The renal presentation was consistent with a tubulointerstitial disease, as suggested by the findings of defective urine-concentrating capacity, moderate polyuria, negative urinalysis, and mild tubular proteinuria. Histology confirmed tubulointerstitial nephritis. Surprising, amyloid was restricted to nonglomerular regions and limited to the renal medulla. This location of apolipoprotein A-I amyloid differs sharply from other systemic amyloidoses that are mainly characterized by glomerular and vascular deposits. The tubulointerstitial nephritis as a result of hereditary apolipoprotein A-I amyloidosis is a rare disease and a challenging diagnosis to recognize. Patients who present with familial tubulointerstitial nephritis associated with liver disease require a high index of suspicion for apolipoprotein A-I amyloidosis.

Background: There is little direct evidence that fibroblasts are involved in the progression of the renal interstitial fibrosis in human glomerulonephritis. With the availability of a new specific marker for fibroblasts, we determined the presence of fibroblasts in kidneys with IgA nephropathy (IgAN) and correlated their numbers with various clinical parameters. In particular, we also prospectively asked if the number of fibroblasts in the renal interstitium correlates with prognosis., Methods: Cells positive for fibroblast-specific protein 1 (FSP1) were localized in renal biopsy specimens using immunohistochemistry with anti-FSP1 antibody. Clinical features were analyzed by one-way analysis of variance (ANOVA) with the Bonferroni correction. To assess the prognostic impact of the number of FSP1+ fibroblasts on renal survival in 142 patients with normal serum creatinine, the relationship between covariates to renal survival were evaluated univariately using the log-rank test and multivariately using Cox proportional hazards., Results: Fibroblasts identified by their expression of FSP1 accumulate in areas showing severe interstitial fibrosis. Some tubular epithelial cells undergoing epithelial-mesenchymal transition (EMT) in fibrotic areas also express FSP1. Numbers of FSP1+ fibroblasts directly correlate with serum creatinine (r = 0.74, P < 0.0001) and inversely correlate with estimated creatinine clearance (r = -0.54, P < 0.0001), and by multivariate analysis, the clinical factors influencing renal survival are urinary protein excretion [> or = 1.0 g/day, relative risk (RR) = 4.20, P= 0.032], hypertension (RR 5.85, P = 0.0027), and > or = 20 FSP1+ fibroblasts per high power field (HPF) (RR 7.39, P = 0.0015). Staining for FSP1+ fibroblasts is largely nonoverlapping with alpha-smooth muscle actin+ (alpha-SMA) cells in the interstitium., Conclusion: The target protein FSP1 identifies human fibroblasts and tubular epithelium undergoing EMT, and distinguishes them from the diaspora of alpha-SMA+ vascular smooth muscle cells. FSP1+ fibroblasts are critically related to the progression of IgAN; consequently, staining FSP1 in renal biopsy specimens provides a valuable histologic index of progression.

Prompt diagnosis and treatment with corticosteroids of the tubulointerstitial nephritis with uveitis (TINU) syndrome may assist in the preservation of renal function. We present a case illustrating the characteristic clinical features of this syndrome. Gallium scintigraphy assisted in the diagnosis and management of this case, which was complicated by relapsing pyelonephritis.

We report a case of tubulointerstitial nephritis and uveitis (TINU) syndrome in an adult male. A 40-year-old man was found to have bilateral anterior uveitis and mild renal insufficiency with high urinary beta-2 microglobulin. Work up for connective tissue and infectious diseases were negative. His kidney function normalized spontaneously and remained normal at 1 year without intervention. Uveitis responded completely to local corticosteroid treatment and has not recurred.

Six of 15 (40%) inactive medical records of adult black howler monkeys (Alouatta caraya) at one zoological institution included either a pre- or postmortem diagnosis of renal disease. In these six cases, significantly abnormal hematologic and serum chemistry values were reported at onset of azotemia, onset of clinical signs, and at euthanasia. Average age of onset of azotemia was 14.8 +/- 2.9 yr, with clinical signs of disease noted at 17 +/- 4.7 yr. In four of the cases (66.6%), azotemia was documented earlier than the onset of clinical signs of renal disease. Average duration of clinical disease was 2.83 +/- 1.6 yr, with an average age at euthanasia of 18 +/- 4.7 yr. Chronic tubulointerstitial nephritis with secondary glomerular sclerosis was present in all cases. Thirteen of an additional 20 institutions in the United States that have held Alouatta caraya responded to a survey for prevalence of renal disease. These institutions showed a lower prevalence (15.1%) of renal disease in complete, inactive records, a higher prevalence of glomerulonephritis, and similar significant clinicopathologic values.

NSAIDs are commonly used drugs. Even with the advent of selective COX-2 inhibitors, nephrotoxicity still remains a concern. The adverse effects of NSAIDs are mediated via inhibition of prostaglandin synthesis from arachidonic acid by non-specific blocking of the enzyme cyclooxygenase leading to vasoconstriction and reversible mild renal impairment in volume contracted states. When unopposed, this may lead to acute tubular necrosis and acute renal failure. NSAIDs also produce interstitial nephritis with or without nephrotic syndrome secondary to minimal change disease. Although this presents as acute renal failure, it can progress in some cases to chronic renal failure. Papillary necrosis has been incriminated in the development of chronic renal failure secondary to NSAIDs. In patients on long term NSAIDs without acute or chronic renal failure, subclinical renal dysfunction such as reduced creatinine clearance and impaired urine concentrating ability has been shown to be present. Although this sub-clinical dysfunction is reversible on withdrawal of NSAIDs, some reports have suggested a persistent residual dysfunction. Even with a wide range of NSAIDs at our disposal, a renal safe NSAID is yet to be discovered.

Ochratoxin A (OTA) is a nephrotoxic mycotoxin considered to be the causal agent of the Balkan endemic nephropathy (BEN). In Tunisia, a chronic interstitial nephropathy (CIN) of unknown aetiology, resembling BEN, has been characterised wherein OTA seems to be implicated too. However, despite the considerable number of investigations conducted so far, the role of OTA in the outcome of this human nephropathy is still uncertain. In this study, an attempt is being made to consolidate the link between OTA and the Tunisian CIN of unknown aetiology. Blood OTA and beta(2)-microglobulinuria levels were measured in several groups of healthy individuals and patients having different renal diseases of known and unknown aetiologies (100 nephropathy patients and 40 healthy subjects). The high blood OTA and beta(2)-microglobulinuria levels seem to be strongly associated to the CIN of unknown aetiology. Our results support the involvement of this nephrotoxic agent in the outcome of this particular human nephropathy and underline furthermore the importance of beta(2)-microglobulinuria in the characterization of this disease.

Background & Aims: This study was performed to quantify the risk of renal disease in patients using aminosalicylates (5-ASA)., Methods: Data from the United Kingdom General Practice Research Database were used to estimate the incidence of renal disease in adult patients with inflammatory bowel disease (IBD) or prescription for 5-ASA and in patients without IBD. In a nested case-control analysis, each case of renal disease was matched to 5 controls., Results: Among the 19,025 5-ASA users with IBD, 130 patients developed renal disease (incidence rate of 0.17 cases per 100 patients per year). The incidence among patients with IBD but without 5-ASA use was 0.25 and among patients without IBD was 0.08. In the case-control analysis, the crude odds ratio (OR) for renal disease in current 5-ASA users was 1.60 (95% confidence interval [95% CI]: 1.14-2.26); the adjusted OR was 0.86 (95% CI: 0.53-1.41). For recent users, the crude OR was 4.18 (95% CI: 2.59-6.76) and adjusted OR 2.48 (95% CI: 1.33-4.61); for past users (last prescription more than 12 months before), 1.71 (95% CI: 1.09-2.70) and 0.99 (95% CI: 0.55-1.76), respectively. Although the numbers were small, mesalazine and sulfasalazine users had comparable risks (crude OR for current and recent users of OR 2.08 [95% CI: 1.44-3.01] and 1.84 [95% CI: 1.20-2.82], respectively). In only a few records was renal disease attributed to interstitial nephritis or 5-ASA use., Conclusions: Users of 5-ASA have an increased risk of renal disease that may be partly attributable to the underlying disease. Although renal disease is a recognized adverse effect of 5-ASA, the incidence appears to be low and does not appear to be related to either the dose or type of 5-ASA used.

Background: BK virus (BKV) associated interstitial nephritis is a complication in renal transplantation recipients. Its incidence is controversial. The aim of the present study is to determine the incidence of histopathologic evidence of BKV-infection in a single centre., Materials and Methods: Renal allograft tissue samples (n = 838) from 526 patients undergoing renal transplant were evaluated by light microscopy. Polymerase chain reaction (PCR) assay for BKV DNA was performed in 41 microdissected cell populations from cases with viral inclusions, cases with other nuclear changes, and cases without nuclear changes., Results: Polyomavirus-inclusions were identified in six cases (five with interstitial nephritis and other one with only urothelial infection). In one case with interstitial nephritis the DNA was degraded. PCR confirmed BKV infection in the other five and was negative in cases without inclusions., Conclusions: Five patterns of inclusions bodies are observed and they appear to be characteristic. PCR assay seemingly have a high specificity for BKV detection and it does not usually detect latent viral infection.

Interstitial nephritis is an uncommon cause of acute renal failure. Reported incidence varies widely in the literature and may depend on several factors i.e. geographical location, diagnostic criteria, dietary, environmental factors and therapeutic practices. This is a retrospective study of biopsy proven interstitial nephritis in National University Hospital Singapore. We report five cases out of a total of 349 biopsies carried out during a five-year period between September 1997 and August 2002. Four patients presented acutely with fever and or cough. In four patients, there was exposure to traditional Chinese medications and/or drugs. Renal failure in four out of the five patients progressed rapidly, three of whom required dialysis. One patient was treated with steroids. Renal function recovered in all patients with one patient who had significant residual renal impairment after one month.

The authors report a case of tubulointerstitial nephritis and uveitis (TINU syndrome) in a 48-year-old woman. The patient's ocular symptoms (relapsing bilateral uveitis) began 4 months before the renal disease was diagnosed and were treated successfully with local steroid therapy. The main baseline laboratory findings were anemia, a rapid sedimentation rate, and a decreased renal function. Urinalysis results showed mild proteinuria and some hyaline and hyaline-granular casts. Immunoglobulin (Ig) G and IgM antibodies to Epstein-Barr virus (EBV) were present. The renal biopsy showed interstitial lymphocytes and infiltration by rare plasma cells, tubular atrophy without granulomas, and slight expansion of the mesangium; electronic microscopy showed rare electron-dense deposits in the mesangium; no vascular alterations were seen, and immunofluorescent staining was uniformly negative. X-ray of the pelvis showed bilateral sacroileitis, which has been previously described in only 1 case of TINU syndrome; human leukocyte antigen B27 was negative. After 6 months without any therapy, all laboratory findings were normal; after 30 months, renal function was still normal, uveitis had not relapsed, but sacroiliac involvement was still present; EBV-viral capsid antigen (VCA) IgM were still high (28 UA/mL), and the EBV IgG titers were increased (VCA>170, EBV-nuclear antigen 108 UA/mL). This case confirms that this rare entity, originally observed in children, may occur and have a favorable spontaneous renal outcome also in the adult; EBV may play a role, as previously suggested. This is, to the authors' knowledge, the first reported case of TINU syndrome with the association of a well-documented bilateral sacroileitis.

Background: Tubulointerstitial damage is recognized as a determinant of the prognosis of kidney disease. Various types of viral infection have been reported to induce tubulointerstitial lesions; however, that caused by hepatitis C virus (HCV) remains unclear, although glomerular lesions caused by this viral infection have been well documented., Methods: To identify any association, we retrospectively investigated 320 patients who underwent renal biopsy and did not have extrarenal diseases causing tubulointerstitial nephritis., Results: Of these patients, 13 patients had HCV infection and 307 patients did not. In a case-control study, HCV infection showed a significant association with the prevalence of tubulointerstitial injury. To offset the secondary tubulointerstitial change caused by advanced glomerulopathy, we performed a glomerular stage-matched comparison of patients with membranous nephropathy (MN). Nine patients with MN among the 13 HCV-infected patients and 18 HCV-negative patients with electron microscopic glomerular stage-matched MN were randomly selected from the overall pool of patients. Comparing areas of interstitial fibrosis and inflammatory cell infiltration, both were greater in HCV-infected than HCV-negative patients. In biopsy tissues from HCV-infected patients, positive signal for HCV was observed in the perinuclear area of tubular epithelial cells and infiltrating cells on immunohistochemistry and in situ hybridization. By a strand-specific reverse-transcription polymerase chain reaction for HCV, both genomic- and replicative-strand RNA were detected in renal tissues., Conclusion: These results suggest that HCV infection is a potent pathogenic factor of tubulointerstitial injury.

In this study we have analyzed incidence, causes and clinical course of ARF due to primary intrarenal disease other than acute tubular necrosis. Thousand hundred and twenty two cases of ARF of diverse etiology were studied over a period of 16 years; July 1984 to Dec, 1999. Surgical ARF 231 (20.6%) were not included in the present study. Intrinsic renal diseases were responsible for ARF in 891 (79.4%) of cases. The most common intrinsic renal diseases 705 (79.4%) causing ARF were ischemic/toxic acute tubular necrosis, but not included in this study. Acute renal failure was related to acute glomerulonephritis (9.3%), acute interstitial nephritis (7%), and renal cortical necrosis in (4.6%) of cases. Therefore intrinsic renal diseases other than ATN were the causative factor for acute renal failure in 186 (20.8%) patients in our study. Crescentic (51.8%) and endocapillary proliferative glomerulonephritis (34.9%), were the main glomerular diseases responsible for ARF and 75.9% of GN was related to infectious etiology. Fifty three percent of acute interstitial nephritis was drug induced and in 25 (40%) patients it was related to an infectious etiology. Renal cortical necrosis due to HUS was observed in 16 (39%) children and majority (76.47%) of the cases had a diarrhoeal prodrome. Obstetrical complications were the main causes (61%) of cortical necrosis in adults with acute renal failure. Thus, intrinsic renal diseases other than ATN were responsible for ARF in 186 (20.8%) cases. Post-infectious glomerulonephritis, acute interstitial nephritis and renal cortical necrosis (complicating HUS in children and obstetrical complications in adult) are the main causes of acute renal failure in our study. Both acute GN and interstitial nephritis had excellent prognosis, however renal cortical necrosis was associated with a very high mortality.

Ochratoxin A (OTA) is a nephrotoxic mycotoxin that is being increasingly considered as the main causal agent of Balkan endemic nephropathy (BEN), a fatal kidney disease associated with the end stage of urothelial tumours. However, despite the considerable amount of data, it is still controversial whether OTA plays a causative or only a subordinate role in the induction of this human nephropathy. Tunisia for years had to confront a very similar human nephropathy, which is tentatively called chronic interstitial nephropathy of unknown cause. This study tends firstly to consolidate the suspected link between this Tunisian chronic interstitial nephropathy (CIN) of unknown cause and the presence of OTA in the blood and food of such patients, and second to enlighten the endemic character of this particular nephropathy. Therefore, in four consecutive inquiries, performed within the period 1991-2000, blood and food OTA contaminations were assayed and compared for 954 nephropathy patients and 205 healthy subjects from the Tunisian general population. This survey was also designed to show that, although the whole population is likely to be exposed to OTA, specific people living in conditions showing similarities with the Balkans do have a kidney disease apparently linked to ochratoxin in food. The results showed that the highest incidences were found in patients with CIN of unknown cause. Indeed, the percentages of OTA-positive samples ranged from 93% to 100%, whereas it was only from 62% to 82% in healthy subjects. Mean OTA concentrations were also higher in patients with CIN of unknown cause than in controls (44.4 +/- 19 microg/L to 55.6 +/- 19 microg/L as opposed to 1.22 +/- 1.2 microg/L to 3.35 +/- 2.32 microg/L, respectively). This study emphasizes further the implication of OTA on this particular human nephropathy and underlines the probable causative role of OTA in the onset of this disease. It is important to note that the highest levels of food OTA contamination were found in the group presenting with CIN of unknown cause, indicating that, similar to the case in the Balkans, people are exposed to OTA essentially by their food.

The commonest clinical presentation of both immunoalergic interstitial nephritis (IIN) and atheroembolic renal disease (ATD) is an acute renal failure accompanied by skin lesions and eosinophilia. As a consequence, differential diagnosis between both entities is often very difficult. We have performed a comparative retrospective study of those patients diagnosed as having IIN or ATD in our Hospital in the period 1980-2000. A total of 42 patients have been diagnosed of IIN and 16 of ATD. Demographic data, as well as clinical and laboratory parameters and outcomes of every studied patient were analysed. We found a significantly higher prevalence of male sex (100% vs 57%, p < 0.01), previous history of hypertension (100% vs 55%, p < 0.01), chronic renal insufficiency (56% vs 17%, p < 0.01), ischemic heart disease (56% vs 14%, p < 0.001), peripheral ischemic disease, endovascular procedures (87% vs 7%, p < 0.001) and anticoagulant treatments (25% vs 5%, p < 0.001) among patients with ATD as compared with IIN, respectively. On the contrary, previous infections (45% vs 12%, p < 0.01) and exposure to new drugs (100% vs 40%, p < 0.001) were significantly more frequent among IIN patients in compare with ATD. ATD patients showed skin lesions consisting of livedo reticularis and digital infarcts (63% vs 31%, p < 0.05) accompanied by blood pressure increase (100% vs 24%, p < 0.001), whereas IIN patients showed fever (41% vs 19%, p < 0.05) and cutaneous rash as significant clinical manifestations, respectively. The number of ATD patients with proteinuria > 1 g/24 h was significantly higher, but no differences between both groups in the prevalence of urinary sediment abnormalities were observed. The prevalence of absolute eosinophilia was high in both groups (88% among ATD patients, 64% among IIN patients; pNS). Prognosis of both entities was clearly different: Almost all patients with ATD died (69%) or evolved to end-stage renal failure, whereas most patients with IIN showed a recovery of renal function after withdrawal of responsible drugs and steroid treatment. In summary, the analysis of clinical and laboratory data allows an initial differential diagnosis in patients suspected as having IIN or ATD.

Objective: To examine immunogenetic and clinical features in a series of patients with the idiopathic tubulointerstitial nephritis and uveitis (TINU) syndrome diagnosed at the single referral hospital for a defined population in Southern Spain., Patients and Methods: Retrospective study of the case records of all patients diagnosed with the TINU syndrome in the Departments of Ophthalmology and Medicine of the Valme University Hospital (Seville, Spain) from January 1996 through October 2000. Patients were included in this study if they had a renal biopsy showing interstitial edema and infiltration by lymphocytes, plasma cells, macrophages, eosinophils, and neutrophils. In these cases fibrosis was occasionally seen, but no glomerular changes were found. In addition, a diagnosis of uveitis by expert ophthalmologists was always required. Underlying diseases, which might be responsible for the renal or ocular manifestations, were excluded. Patients were HLA-DRB1 genotyped from DNA by using molecular-based methods., Results: Six patients (4 females) fulfilled the definitions described above. Four were younger than 18 years. In addition to tubulointerstitial nephritis, non-granulomatous uveitis (anterior or panuveitis) associated with low visual acuity was present at the time of diagnosis. Leukocytosis and increase of acute phase reactants were also commonly observed at the time of diagnosis. Topical and oral corticosteroids were prescribed to all the patients. Cyclosporine A therapy was required in 2 cases. After a 2.5-year median follow-up, visual acuity had improved in all cases. Of note, 4 of 6 patients carried the HLA-DRB1*01 allele., Conclusion: The TINU syndrome should be considered in the differential diagnosis of patients presenting with visual and renal manifestations. The presence of renal dysfunction in patients with uveitis may be of some help, as a warning sign, for the recognition of patients who require a rapid diagnosis and therapy. In Southern Spain, the TINU syndrome appears to be associated with HLA-DRB1*01 allele., (Copyright 2002, Elsevier Science (USA))

Background: Cyclosporine (CsA) is effective for the treatment of children with steroid-dependent and -resistant nephrotic syndrome (NS), but it can result in chronic CsA nephrotoxicity including CsA-induced tubulointerstitial lesions. The factors responsible for the development of CsA-induced tubulointerstitial lesions are unknown., Methods: To identify the risk factors for the development of CsA-induced tubulointerstitial lesions in children with minimal change NS who had been treated with long-term moderate-dose CsA, we compared several clinical and laboratory factors of 37 patients with and without CsA-induced tubulointerstitial lesions by the Mann-Whitney U test, Fisher's exact test, and stepwise logistic-regression analysis., Results: Thirteen patients had CsA-induced tubulointerstitial lesions and 24 patients had none. Among clinical and laboratory factors, the duration of CsA treatment (P = 0.003) and the duration of heavy proteinuria during CsA treatment (P = 0.024) were related to the development of CsA-induced tubulointerstitial lesions as determined by the univariate analyses. Indeed, CsA-induced tubulointerstitial lesions were found in 2 of 18 (11%) patients who had been treated with CsA for less than 24 months, but in 11 of 19 patients (58%) who had been treated for more than 24 months (P = 0.005). They were also found in 4 of 23 patients (17%) who had heavy proteinuria for less than 30 days during CsA treatment, but in 9 of 14 patients (64%) who had heavy proteinuria for more than 30 days (P = 0.006). Stepwise logistic-regression analysis revealed that the duration of CsA treatment for more than 24 months (chi2 = 6.203, P = 0.013) and the duration of heavy proteinuria during CsA treatment for more than 30 days (chi2 = 5.871, P = 0.015) were independent risk factors for the development of CsA-induced tubulointerstitial lesions., Conclusions: Duration of the CsA treatment and the duration of heavy proteinuria during CsA treatment were independent significant risk factors for the development of CsA-induced tubulointerstitial lesions in children with MCNS who had been treated with long-term moderate-dose CsA.

With improvements in short-term kidney graft survival, focus has shifted towards long-term survival. There has also been a substantial improvement in long-term survival as measured by kidney half-life. Long-term graft failure is secondary to chronic allograft nephropathy (CAN), recurrent disease, and death with a functioning graft. CAN is secondary to a combination of chronic rejection, chronic cyclosporine toxicity, and/or donor kidney disease. Risk factors for chronic rejection have been attributed to both immunological and nonimmunological causes. With a marked reduction in acute rejection rates-an important risk factor for CAN-there is a substantial improvement in kidney half-life. There are still nonimmunological factors, such as donor age, that adversely affect long-term graft survival. In addition, African-American recipients continue to have a shorter graft half-life. Recurrent disease is becoming an important cause of late graft failure. Despite the introduction of various potent immunosuppressive agents, there has been little or no impact on the prevalence as well as progression of recurrent diasease. With the reduction of acute rejection rates and improved short- and long-term graft survival, further improvements of long-term graft survival will be an important focus in the 21st century.

Background/aim: Nephropathy after ingestion of Chinese herbs is known as a rapidly progressive form of interstitial renal fibrosis after a slimming regimen containing aristolochic acid that was identified first in Belgium. Intake of traditional Chinese herbal medicines is very popular in Taiwan. So we looked for similar cases in our hospital., Methods: From 1994 to 1998, we observed 20 Taiwanese patients who underwent renal biopsy for rapidly progressive renal failure of unknown origin. The medical history of these patients gave no clue to the origin of renal impairment, except for the administration of Chinese herbs before the development of renal failure in all cases., Results: Although these patients took herbal medications from various sources for different purposes, their renal biopsy specimens showed strikingly similar histological patterns: extensive paucicellular interstitial fibrosis and tubular atrophy, but the glomeruli were apparently intact. They also had similar clinical features, such as a nearly normal blood pressure, obvious anemia, insignificant edema, low-grade proteinuria, and glucosuria. The renal function declined rapidly in most cases; 15 patients underwent dialysis within 3 months of renal biopsy, and 7 patients received emergency dialysis when they first came to our hospital. On clinical and morphological grounds, the nephropathy in our patients appears similar to Chinese herb nephropathy., Conclusions: Because of the diversity of the herbal regimens used, in addition to aristolochic acid, other unidentified phytotoxins may also play a role in this particular disease entity. There is a strong relation between rapidly progressive interstitial renal fibrosis and the consumption of Chinese herbs., (Copyright 2001 S. Karger AG, Basel)

A retrospective histopathological study was carried out on tissues of 283 raccoons from 5 different geographical locations for presence of interstitial nephritis and renal leptospirosis. Results of this study indicate that although interstitial nephritis was common in raccoons from all locations, the presence of renal leptospiral spirochetes was not.

Objective: To analyze the characteristics of tubulointerstitial lesions (TIL) in IgA nephropathy (IgAN)., Methods: The pathologic and clinical materials of 609 IgAN patients were analyzed., Results: (1) Prevalence characteristics of TIL: Among all the patients, these with mild TIL accounted for 47.1%, moderate TIL 21.7%, severe TIL was about 16.6% and these without TIL 14.6%. (2) Relationship between TIL and the clinical findings: With increase of the severity of TIL, hypertension became worse and the level of proteinuria increased gradually. On the contrary, serum albumin decreased and renal function degraded. (3) Relationship between TIL and the pathologic findings: With increase of the severity of TIL, the scores of vascular lesion, total glomerular lesion, hypercellularity and glomerulosclerosis increased gradually. Moreover, when the glomerular lesion and vascular lesion became worse, the severity of TIL also increased. The relationship with the crescents was different, the score of the presence of crescents was highest when TIL was moderate in severity; it would not increase when TIL was severe., Conclusion: With the increase of the severity of TIL, the condition of IgAN patients became worse. TIL may be one of the key factors for the prognosis of IgAN. TIL is closely related to the severity of glomerular and vascular lesions, and these lesions may further lead to the development of TIL.

The pathogenesis of tubulointerstitial nephritis and uveitis (TINU) syndrome remains unknown, but T cell-mediated immune response has been postulated to play a role. On the other hand, TINU syndrome is characterized by hypergammaglobulinemia and high serum immunoglobulin G (IgG) levels, suggesting an involvement of humoral immunity. We describe a case of TINU syndrome in a 13-year-old girl with multiple tubular dysfunctions including renal glucosuria, tubular proteinuria, phosphaturia, uricosuria, and concentrating and acidifying defect. IgG antibody from her serum was reactive against 125-kDa human kidney protein. Immunofluorescence study using mouse kidney revealed that the antibody was against cortical renal tubular cells. The antibody disappeared as the renal symptoms resolved. We suggest that IgG antibody may contribute to tubular dysfunction in some patients with TINU syndrome.

Analgesic abuse is related to a specific form of interstitial nephritis, but the exact nature of the causal agent remains controversial and this has resulted in differences in regulation. In Flanders, the free sale of phenacetin was banned, but the consumption of other combined analgesics remained free. In New South Wales, phenacetin was also banned, but 2 yr later the sales of all combined analgesics were also prohibited. This study compared the evolution of end-stage renal disease as a result of analgesic nephropathy (AN) in these two high-endemic regions with different legislation. In both regions, the time trend of the age-specific incidence of end-stage renal disease as a result of AN is similar in the age group 45 to 54 yr. In all age groups combined, the time trend of the percentage of AN among the patients admitted for renal replacement therapy is also similar. This finding does not support the hypothesis that non-phenacetin mixed analgesics play a significant role in the occurrence of AN.

Background: Chronic renal failure (CRF) is a complex phenotype that results from an underlying kidney disease and superimposing environmental and genetic factors. The aim of our study was to evaluate the role of polymorphisms in the genes encoding for components of the renin-angiotensin system (RAS) in the development and/or progression of CRF., Methods: Two hundred forty-seven family trios (patients with CRF and both parents; 120 with primary chronic glomerulonephritis, 80 with interstitial nephritis, and 47 with type 1 diabetes with nephropathy) were examined, and transmission/disequilibrium test (TDT) was used to evaluate allele transmission from heterozygous parents to affected offspring., Results: The D allele of the angiotensin I-converting enzyme (ACE) gene insertion/deletion polymorphism was transmitted significantly more frequently than expected for no association among all examined trios and in the subgroup of patients with interstitial nephritis. The angiotensinogen 235T allele was transmitted significantly more frequently to patients with CRF than expected for no association, but the effect was seen only in patients with interstitial nephritis. The presence of the DD or ID genotype was associated with a faster rate of decline of renal function, which was not observed for the angiotensinogen M235T polymorphism. For chymase gene and angiotensin II receptor type 1 gene, allele transmission did not deviate significantly from a random proportion of 50:50%., Conclusions: The results of this study suggest that ACE gene insertion/deletion and angiotensinogen M235T polymorphisms contribute to the increased risk for the development of CRF, but the magnitude of the effect within subsets of patients with specific etiologies of CRF must be evaluated further.

Detailed histopathological and immunohistochemical studies were carried out on 24 cetaceans, 17 of which were striped dolphins (Stenella coeruleoalba), four bottlenose dolphins (Tursiops truncatus) and three Risso's dolphins (Grampus griseus), all found stranded on the Italian coast between 1990 and 1997. The most frequently detected lesions were chronic pneumonia (73.7% of the examined lungs), focal chronic pancreatitis (71.4%), non-purulent encephalitis (50%), chronic hepatitis (42.1%), and chronic focal interstitial nephritis (31.2%). The skin and the subcutaneous panniculus were often (33.3%) affected by parasitic diseases (Phyllobothrium delphini and Pennella sp.). An appreciable percentage of animals showed lymphoid depletion in their lymphatic organs (47.2%), as well as a high rate of parasitic infestations in their alimentary tracts (25%).

In 1980, the first Moroccan hemodialysis center was founded in Casablanca. The number of centers has been increasing since then, to reach 61 centers to wards the of 1996. There are 1800 hemodialysed (males 59%, females 41%) with and average age of 51 +/- 4 years. In about one third of the cases, the cause of the end stage renal failure remains unknown. However, chronic glomerulonephritis comes at the head of known causes (25%), followed by interstitial nephritis (19%). A temporary vascular access (catheter) was necessary in 81% of cases when dialysis has started in emergency in 61% of patients. Infections were the most frequent complications (21%) namely septicaemia (8%) and tuberculosis (7%). The vaccination against hepatitis B virus is done systematically in all the centers, and the number of chronic carriers of HBS Ag is about 7%. Further more, serological C virus is positive in 40% of the hemodialysed patients. Cardio-vascular complications were dominated by percarditis (13%) especially at the beginning of the dialysis. Anaemia remains very frequent and often very important requiring multiple blood transfusions (35%) in the absence of erythropoietin treatment. The death rate, which is very difficult to estimate, is of about 18%. Peritoneal dialysis was used in 50 patients but only four patient continued on peritoneal dialysis therapy. 108 patients were transplanted (23 cases in Morocco, 85 in other countries) with a waiting list of 0 to 12 years. Hemodialysed Moroccan's population is characterised by the high number of unknown causes and the gravity of the admission stage. A renal effort in prophylactic should be performed to avoid certain causes of renal failure.