Prognosis of proliferative lupus nephritis subsets in the Louvain Lupus Nephritis inception Cohort.

OBJECTIVE: The objective of this paper is to evaluate whether the different International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes of proliferative lupus nephritis (LN) have a distinct baseline presentation, short-term response to immunosuppression (IS) and long-term prognosis. METHODS: Ninety-eight patients with new onset (first renal biopsy) ISN/RPS proliferative LN (Class III: n=24; IV-S: n=23; IV-G: n=51) were diagnosed at our institution between 1995 and 2012 (Louvain Lupus Nephritis inception Cohort). Their baseline renal parameters, primary response to IS at one year, survival and long-term renal outcome (mean follow-up: 77 months) were compared. RESULTS: At baseline, serum creatinine and 24-hour proteinuria were higher in Class IV-G, as was activity index on renal biopsy in Class IV-S and IV-G compared to III. Upon treatment, renal parameters improved with the same kinetics and to the same extent in the three pathological classes. On repeat renal biopsies (n=43), activity indices dropped similarly. Poor outcomes (death, end-stage renal disease, renal impairment defined by an eGFR <60 ml/min/1.73 m(2)) did not statistically differ between groups, although there was a trend toward more renal impairment at follow-up in Class IV-G compared to IV-S and III. Finally, the presence of even mild chronic lesions on baseline biopsy was clearly predictive of late renal outcome. CONCLUSION: Subsetting proliferative LN into Class III, IV-S and IV-G provides less clinically discriminant prognostic information than baseline chronicity index.

Pre-terminal renal insufficiency in a patient with enteric hyperoxaluria: effect of medical management on renal function.

Enteric hyperoxaluria causes tubular deposition calcium oxalate crystals and severe chronic interstitial nephritis. We describe a patient with pre-terminal renal failure due to oxalate nephropathy after ileal resection. Increased oral hydration, low oxalate diet, and oral calcium carbonate and potassium citrate supplements resulted in a significant improvement of renal function. During the three-year follow-up, urinary oxalate concentration was repeatedly reduced below the crystallization threshold and serum creatinine decreased from 4.5 to 1.7 mg/dL. This case illustrates the benefit of combining and optimizing dietary and medical management in enteric hyperoxaluria, even in patients with advanced chronic kidney disease.

Thrombotic microangiopathy induced by long-term interferon-ß therapy for multiple sclerosis: a case report.

We report the case of a 53-year-old woman treated for 8 years with Betaferon® (interferon-ß-1b), who developed mild renal failure with hypertension, proteinuria and glomerular hematuria. Kidney biopsy was consistent with thrombotic microangiopathy (TMA). Considering the strong evidence of interferon-α causing TMA and the numerous immunomodulatory activities shared by INF-α and -ß, we incriminated Betaferon as the etiological agent of TMA in our patient. To our knowledge, it is the first time such an association has been published.

Secondary retroperitoneal teratoma.

Retroperitonal teratomas are rare. We report on a case of a retroperitoneal secondary localisation of a gonadal teratoma in a patient who had developed primary testicular teratoma 12 years previously. The retroperitoneal mass was detected with an abdominal CT requested for the management of a non-specific abdominal pain. CT and MRI examinations showed cystic retroperitoneal masses combined with calcifications and peripheral enhancement. Review of the literature is presented, including the common differential diagnoses to be considered.

Retroperitoneal, mesenteric and multifocal fibrosis: review of their aetiopathogenesis. A possible role of adipocytes as in Crohn's disease?

First observed during an autopsy by Simpson in 1867 as a cause of hydronephrosis, retroperitoneal fibrosis became a medical topic after the detailed report of two cases by Ormond in 1948. Initially considered to be chiefly an urological disease, it appeared progressively that it could possibly be a systemic disease because of its occasional association with inflammatory fibrosing processes in other sites of the body or with clinical and biological manifestations of hypersensitivity or autoimmunity. Mesenteric panniculitis and mesenteric fibrosis may occur independently or, occasionally, in association with retroperitoneal fibrosis. One third of the cases of retroperitoneal fibrosis can be attributed to specific causes. That the other cases (idiopathic retroperitoneal fibrosis) could be manifestations of an immunological (systemic) process with vasculitis is generally accepted. The authors present a survey of the various possible morphological aspects of the disease and a review of its aetiopathogenesis. Idiopathic retroperitoneal fibrosis is usually characterized by an overproduction of fibro-inflammatory tissue; however in few cases as well as in mesenteric panniculitis, extensive development of fatty tissue may also occur. The authors suggest that an initial proliferation of adipocytes, considered to account for the fat hyperplasia adjacent to Crohn's ileitis, could also play a role in the pathogenesis of the inflammatory fibrosing process in some cases of mesenteric and retroperitoneal fibrosis.

Renal insufficiency, a frequent complication with age in oral-facial-digital syndrome type I.

The oral-facial-digital syndrome type I (OFD I) is characterized by multiple congenital malformations of the face, oral cavity and digits. A polycystic kidney disease (PKD) is found in about one-third of patients but long-term outcome and complications are not well described in the international literature. Renal findings have been retrospectively collected in a cohort of 34 females all carrying a pathogenic mutation in the OFD1 gene with ages ranging from 1 to 65 years. Twelve patients presented with PKD - 11/16 (69%) if only adults were considered -with a median age at diagnosis of 29 years [IQR (interquartile range) = (23.5-38)]. Among them, 10 also presented with renal impairment and 6 were grafted (median age = 38 years [IQR = (25-48)]. One grafted patient under immunosuppressive treatment died from a tumor originated from a native kidney. The probability to develop renal failure was estimated to be more than 50% after the age of 36 years. Besides, neither genotype-phenotype correlation nor clinical predictive association with renal failure could be evidenced. These data reveal an unsuspected high incidence rate of the renal impairment outcome in OFD I syndrome. A systematic ultrasound (US) and renal function follow-up is therefore highly recommended for all OFD I patients.

The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide.

OBJECTIVE: To update the follow-up of the Euro-Lupus Nephritis Trial (ELNT), a randomised prospective trial comparing low-dose (LD) and high-dose (HD) intravenous (IV) cyclophosphamide (CY) followed by azathioprine (AZA) as treatment for proliferative lupus nephritis. PATIENTS AND METHODS: Data for survival and kidney function were prospectively collected during a 10-year period for the 90 patients randomised in the ELNT, except in 6 lost to follow-up. RESULTS: Death, sustained doubling of serum creatinine and end-stage renal disease rates did not differ between the LD and HD group (5/44 (11%) vs 2/46 (4%), 6/44 (14%) vs 5/46 (11%) and 2/44 (5%) vs 4/46 (9%), respectively) nor did mean serum creatinine, 24 h proteinuria and damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. After 10 years of follow-up, the positive predictive value for a good outcome of an early drop in proteinuria in response to initial immunosuppressive therapy was confirmed. CONCLUSION: The data confirm that a LD IVCY regimen followed by AZA-the "Euro-Lupus regimen"-achieves good clinical results in the very long term.

Acute venous thrombosis of a renal transplant: early detection with color Doppler sonography.

The observation of a recent case of an acute venous thrombosis of a renal transplant is the opportunity to review and present the role of color Doppler sonography for the early detection of such a severe and uncommon complication.

Tenofovir-related acute kidney injury and proximal tubule dysfunction precipitated by diclofenac: a case of drug-drug interaction.

We describe an HIV1-positive patient under long-term tenofovir treatment who developed a severe, biopsy-proven, acute tubular necrosis with proximal tubule (PT) dysfunction, precipitated by the very recent start of diclofenac, a nonsteroidal antiinflammatory drug (NSAID). Recent studies show that NSAIDs not only alter glomerular filtration but also multidrug resistance protein (MRP) 4-mediated PT secretion of several substrates. Since the patient tolerated tenofovir well for several years prior to diclofenac use, our observation suggests that diclofenac interfered with tenofovir clearance, thereby favoring its nephrotoxicity. NSAIDs should be avoided in patients under tenofovir.

An easily overlooked iatrogenic cause of renal failure.

We report moderate renal failure in a 50-year-old man with a history of recent colonoscopy after oral sodium phosphate purgative use. We initially missed the correct diagnosis, but renal biopsy revealed signs of acute phosphate nephropathy. The patient had residual renal impairment at 8-month follow-up. Greater awareness of this complication is needed amongst health care professionals. The preventive strategies are discussed.

Pauci-immune necrotizing and crescentic glomerulonephritis in a patient with systemic lupus erythematosus.

We report a case of pauci-immune proliferative necrotizing and crescentic glomerulonephritis in a patient with systemic lupus erythematosus (SLE) who presented with a nephrotic syndrome, while SLE was clinically and serologically quiescent. Immunofluorescence and electron microscopy examination of the kidney biopsy failed to reveal any significant deposit of immunoglobulins as well as of complement C3 and C1q, excluding lupus nephritis as the determinant of crescentic glomerulonephritis. Anti-myeloperoxydase (MPO) as well as anti-proteinase 3 (PR3) antibodies were absent in the serum. An immunosuppressive regimen including corticosteroids and IV cyclophosphamide led to a dramatic decrease of proteinuria. We conclude that necrotizing glomerulonephritis unrelated to lupus nephritis may occur in a patient with quiescent SLE. An underlying dysfunction of cell-mediated immunity might explain the association of pauci-immune crescentic glomerulonephritis and SLE.

Acute interstitial nephritis after cocaine sniffing.

We report the case of a 42-year-old man who developed biopsy-confirmed acute interstitial nephritis (AIN) after cocaine sniffing. He required a few hemodialysis sessions but fully recovered within 3 weeks after cocaine withdrawal and a short course of corticosteroids. AIN should be recognized as a potential cause of acute renal failure in cocaine users, and a history of cocaine use should be carefully elicited in patients with unexplained AIN.

Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Late-onset primary hyperoxaluria triggered by hypothyroidism and presenting as rapidly progressive renal failure--description of a new mutation.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal metabolic recessive disease, caused by the deficiency of the liver peroxysomal alanine:glyoxylate aminotransferase (AGT), characterized by accumulation of calcium oxalate crystals in kidneys and others organs. We present the case of an elderly woman with PH1, presenting as acute renal failure. Precipitation of calcium oxalate crystals was probably due to amiodarone-induced severe hypothyroidism. Residual AGT activity is associated with the G170R (G630A) mutation. A new mutation of AGT, called R36C, was also discovered; the role of this new mutation is actually not known.

Does site-specific labelling and individual processing of sextant biopsies improve the accuracy of prostate biopsy in predicting pathological stage in patients with T1c prostate cancer?

OBJECTIVE: To evaluate whether individual labelling and processing of the sextant of origin improves the accuracy of prostate biopsy in predicting the final pathological stage after radical prostatectomy in patients with T1c prostate cancer. PATIENTS AND METHODS: The charts of 386 patients treated for prostate cancer by radical prostatectomy between January 1996 and June 1999 were reviewed. In all, 124 patients fulfilled the following inclusion criteria: no abnormality on digital rectal examination (DRE) or transrectal ultrasonography, a prostate specific antigen (PSA) level before biopsy of < or = 20 ng/mL, and prostate cancer diagnosed after one set of random sextant biopsies, with the cores being submitted in six separate containers individually labelled for the sextant of origin. RESULTS: Within this series of patients with a low tumour burden, the preoperative PSA, biopsy Gleason score and unilateral vs bilateral involvement were not significant predictors of disease extension. The percentage of positive cores and the number and topography of positive sextants were both statistically significant predictors of organ-confined disease. Although these two variables appeared to be statistically equivalent on a first analysis in the overall series, a subgroup of patients was identified who benefited from the complete topographical information, i.e. those 52 (42%) patients with a Gleason score of < 7, 25-75% positive biopsies and < or =3 positive sextants. CONCLUSION: These results support the individual labelling of biopsy cores in selected patients with a normal DRE and a moderately elevated PSA, as it helps to better predict the final pathological stage. This substantial benefit outweighs the additional effort by the pathologist.

Lessons from the "Euro-Lupus Cohort".

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Aristolochic acid nephropathy in a Chinese patient: time to abandon the term "Chinese herbs nephropathy"?

The causal role of aristolochic acid (AA) in the so-called Chinese herbs nephropathy (CHN) has been conclusively demonstrated only in the Belgian epidemic. We report a biopsy-proven hypocellular interstitial fibrosing nephropathy in a Chinese patient who had ingested a Chinese herbal preparation bought in Shanghai. The identification of AA in the preparation and of AA-DNA adducts in the kidney tissue unequivocally demonstrates, for the first time, the causal role of AA outside the Belgian epidemic. Because the ingested preparation is very popular in China as an over-the-counter product, our observation raises the possibility that many such cases due to AA might be currently unrecognized in China. AA should be banned from herbal preparations worldwide. All cases of the so-called CHN, in which the causal role of AA has been thoroughly documented, should be further identified as aristolochic acid nephropathy (AAN). The term phytotherapy-associated interstitial nephritis (PAIN) might refer to the other cases associated with phytotherapy without identification, as yet, of the causal agent.

Analyses of DNA adducts formed by ochratoxin A and aristolochic acid in patients with Chinese herbs nephropathy.

Chinese herbs nephropathy (CHN), a unique type of nephropathy has been associated with the intake of weight-reducing pills containing the Chinese herb Aristolochia fangchi. Moreover, an association between the use of A. fangchi and urothelial cancer in CHN patients has been reported indicating that aristolochic acid (AA) the major alkaloid of A. fangchi might be the causal agent. Similarities of CHN to the Balkan endemic nephropathy (BEN) have led to the hypothesis of a common etiological agent for both diseases. Evidence has accumulated that BEN is an environmentally-induced disease strongly associated with the fungal mycotoxin ochratoxin A (OTA). Both, AA and OTA are nephrotoxic and carcinogenic and induce the formation of DNA adducts. As OTA has been suspected as fungal contaminant in the herbal batches used for the preparation of the weight-reducing pills we analysed tissues from CHN patients by the 32P-postlabeling procedure for the presence of DNA adducts related to both OTA and AA exposure. Whereas, AA-specific DNA adducts were detected in all five urinary tract tissues from five patients (total RAL: 32-251 adducts per 10(9) nucleotides), OTA-related DNA adducts were detectable in two kidneys and one ureter only (total RAL: 1.5-3.7 adducts per 10(9) nucleotides). Thus, OTA-related DNA adduct levels were about 50 times lower than AA-DNA adduct levels. In female and male rats that were treated with the slimming regimen in the same way like the CHN patients except that the amount of Chinese herbs was 10 times higher, AA-DNA adducts were found in kidney tissues (total RAL ranging from 51 to 83 adducts per 10(9) nucleotides) but adducts derived from OTA were not observed. These results demonstrate that OTA-related DNA adducts do not play a key role in CHN or CHN-associated urothelial cancer.

Chronic aristolochic acid toxicity in rabbits: a model of Chinese herbs nephropathy?

BACKGROUND: Chinese herbs nephropathy (CHN) is a new type of subacute interstitial nephritis that is attributed to aristolochic acid (AA), which inadvertently has been included in slimming pills. The contribution of other simultaneously prescribed drugs remains disputed. In the present study, the effects of a chronic intake of AA given as a single drug was evaluated through renal histology and function in rabbits. METHODS: Female New Zealand White rabbits were injected intraperitoneally with either 0.1 mg AA/kg or with saline 5 days a week for 17 to 21 months. Body weight, renal function, and urinary excretion of glucose and low molecular weight proteins were monitored prior to sacrifice at the end of the study period. RESULTS: All animals given AA developed renal hypocellular interstitial fibrosis, which was classified into three patterns. Fibrosis was confined to medullary rays (MRs) in pattern I (N = 3), extended to the outer cortical labyrinth (OCL) in pattern II (N = 2), and eventually to the inner cortical labyrinth (ICL) in pattern III (N = 6). Fibrosis in MR and OCL was associated with mainly proximal tubular epithelial cell flattening. All treated animals displayed urothelial atypia. Three of them also developed tumors of the urinary tract. No significant pathologic changes were found in control rabbits. AA-treated animals differed from controls by an impaired growth, increased serum creatinine, glucosuria, tubular proteinuria, and anemia. CONCLUSION: The observed pattern of renal histopathological lesions and disorders of the renal function, as well as urothelial atypia and malignancy, are very reminiscent of CHN. Our observations therefore support a causal role of AA alone in the genesis of this new nephropathy.