Krešimir Galešić

Acute interstitial nephritis due to mesalazine

SUMMARY:  A case of mesalazine‐induced acute interstitial nephritis (AIN) in a 41‐year‐old patient with ulcerative colitis (UC) is reported here. Clinical symptoms such as fever and arthralgia, and laboratory findings such as eosinophilia and renal failure suggested AIN, which was confirmed by biopsy. With withdrawal of mesalazine and intravenous methylprednisolone the patients renal function was recovered. It is observed that early discontinuation of mesalazine is associated with amelioration of interstitial nephritis in most patients, so the recommendation is that patients receiving mesalazine should undergo routine monitoring of renal function. Delayed diagnosis may lead to permanent renal function impairment.

Endothelin-1 and Nitric Oxide in Patients on Chronic Hemodialysis

Aim. To establish the role of endothelin-1 and nitric oxide in the pathogenesis of hypertension in patients on chronic aemodyalisis by correlating endothelin-1 and NO plasma concentrations to the level of arterial hypertension with respect to angiotensin-converting enzyme (ACE) inhibitor therapy. Methods. We determined plasma concentrations of endothelin-1 and NO in patients on chronic hemodialysis (CHD) before and after hemodialysis treatment. The study included 30 CHD patients and 20 healthy participants as controls. Correlation to blood pressure was determined, as well as the effect of ACE inhibitors on the relationship between both endothelin-1 and NO in correlation with arterial hypertension. Main findings.Endothelin-1 plasma concentration was significantly higher in CHD patients before hemodialysis treatment than in healthy controls. Endothelin-1 plasma concentration was also significantly higher in CHD patients after hemodialysis than in healthy controls. There was a significant decrease in endothelin-1 plasma concentration after hemodialysis in comparison with its values before hemodialysis. In CHD patients, a positive correlation was found between endothelin-1 plasma concentration and systolic blood pressure after hemodialysis, irrespective of ACE inhibitors therapy. In CHD patients taking ACE inhibitors, systolic blood pressure increased with increasing endothelin-1 plasma concentration before as well as after hemodialysis. In patients taking ACE inhibitors, there was a tendency for diastolic blood pressure to increase with an increase in endothelin-1 plasma concentration after hemodialysis and to decrease with an increase in NO plasma concentration. Conclusion. NO and endothelin-1 play a significant role in etiology of the hemodynamic changes of blood pressure during the dialysis.

MINIMAL CHANGE DISEASE AND ACUTE TUBULAR NECROSIS CAUSED BY DICLOFENAC

Renal side-effects of anti-inflammatory drugs (NSAID) can be diveded in five clinical syndromes: acute renal failure, acute intersticial nephritis with nephrotic syndrome, electrolyte and fluid disorders, hypertension and analgetic nephropathy.We described one unusual combination of acute tubular necrosis (ATN) and minimal change disease (MCD). Reports of ATN and MCD with nephrotic syndrome caused by NSAID exposure are very rare. This is the first reported case of MCD associated with ATN by Diclofenac. A 53-year-old woman with acute renal failure (creatinine was 716 μ mol/L) and nephrotic syndrome (she was in generalizied oedema and protein excretion was 6.0g/day) was admitted to our hospital. She also had eosinophilia. Her medical history was unremarkable except for nontreated hypertension for five years. Only medication she has been taking was Diclofenac for chronic muscular pain and knee arthropathy. NSAID drugs exert their toxic effect on the kidney by ihibition of prostaglandin synthesis and causing an acute allergic interstitial nephritis. The pathogenesis of NSAID-associated MCD is unclear. NSAID drugs cause inhibiton of cyclooxigenase and shift arachidonic acid toward lipooxygenase pathway, which may result in enhanced production of proinflammatory leukotriens. In addition, lypooxigenase products increase vascular permeability and may contribute by altering glomerular-cappilary barrier. The patient was treated with steroides. The response was excellent with remission of nephrotic syndrome and the normalization of renal excretory function within 6 weeks.

Thrombotic microangiopathy associated with alpha-interferon therapy for chronic myeloid leukaemia.

SUMMARY:  The association of interferon (IFN) therapy with haemolytic uraemic syndrome in patients with chronic myeloid leukaemia (CML) has been reported infrequently. The pathogenesis of the renal lesion in such cases remains unclear. We report the case of a patient with chronic myeloid leukaemia who developed nephrotic syndrome and renal failure while being treated with hydroxyurea and IFN‐α. Renal biopsy showed features of chronic thrombotic microangiopathy. The discontinuation of IFN‐α, and a prompt institution of plasmapheresis and steroids resulted in improvement of the nephrotic syndrome and renal function. These findings suggest that long‐term IFN‐α therapy can induce thrombotic microangiopathy and haemolytic uraemic syndrome in patients with chronic myeloid leukaemia.

Treatment of renal manifestations of ANCA-associated vasculitis

CONTEXT Vasculitis is a clinicopathological entity characterized by inflammation and necrosis of blood vessels. EVIDENCE ACQUISITIONS Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. RESULTS Two major autoantigens for ANCA are myeloperoxidase (MPO) and proteinase 3 (PR3), which are proteins in the primary granules of neutrophils and in the lysosomes of monocytes. They are expressed in mature neutrophils of patients with ANCA, while absent in healthy subjects. CONCLUSIONS The kidney is the most commonly affected vital organ in ANCA-associated vasculitis, and patient outcomes are largely determined by the severity of renal disease at diagnosis and by its response to treatment.

Endothelin-1, big endothelin-1, and nitric oxide in patients with chronic renal disease and hypertension

The complex pathogenesis of chronic renal disease (CRD) depends on endothelin (ET) axis (ETs and ET receptors) and nitric oxide (NO) because of their vasoactive effects and their role in general modulation of vascular homeostasis. Various renal cells synthesize ETs and NO that play a significant role in renal hemodynamics as well as in water and salt excretion via urine. ET‐1 is a strong vasoconstrictor. Besides its vasoactive effects, ET‐1 modulates mitosis and apoptosis in a cell type‐dependent manner, and may play an important role in CRD pathogenesis. The aims of this study were to emphasize the role and interactions of ET‐1, Big ET‐1, and NO in CRD. Concentrations of these vasoactive molecules were measured in plasma/serum and/or urine of 57 patients with diabetic nephropathy (subgroup 1), arterial hypertension (subgroup 2) or CRD with chronic renal insufficiency (subgroup 3), and in healthy control subjects (n=18). In comparison with control group, urine concentration of Big ET‐1 was significantly increased (13.13 pmol/L vs. 11.34 pmol/L; P<0.001) in CRD patients, whereas plasma and urine concentrations of ET‐1 did not differ significantly. NO concentrations were also significantly increased in CRD patients (serum, 72.55 µmol/L; P<0.001, and urine 141.74 µmol/L; P<0.05) as compared to control group. Study results indicated that Big ET‐1 and NO could be useful diagnostic parameters in CRD for their diagnostic sensitivity and diagnostic specificity (Big ET‐1 in urine: 56.1 and 88.9%, and NO in serum: 66.7 and 83.3%, respectively). In addition, Big ET‐1 may prove useful in the differential diagnosis of diabetic nephropathy (78.6% diagnostic sensitivity and 88.9% diagnostic specificity). J. Clin. Lab. Anal. 23:347–356, 2009.

Prognostic significance of glomerular and tubulointerstitial morphometry in idiopathic membranous nephropathy

The purpose of our study was to investigate the prognostic value of clinical and pathological, in particular glomerular and tubulointerstitial morphometric variables in idiopathic membranous nephropathy (IMN). We prospectively followed 60 Caucasian patients diagnosed with idiopathic membranous nephropathy for at least 2 years or until primary outcome (≥50% permanent decrease in estimated glomerular filtration rate or death). Glomerular and tubulointerstitial morphometric variables at the time of renal biopsy were analyzed with respect to this outcome. Univariate analysis revealed that significant negative prognostic factors for this outcome were higher cholesterol and smaller albumin concentrations, higher creatinine and maximal 24-h proteinuria, higher grade of nephroangiosclerosis, higher glomerular basement membrane thickness and glomerulopathy index, higher interstitial fibrosis and tubular atrophy percentage and higher injury score. In multivariate analysis, only the maximal 24-h proteinuria and interstitial fibrosis and tubular atrophy percentage were independent predictors of this outcome. The results suggest that morphometric analysis, mainly quantitative measurement of interstitial fibrosis and tubular atrophy percentage, injury score, glomerular basement membrane thickness and glomerulopathy index could be used as an additional method for risk stratification of patients with idiopathic membranous nephropathy.

Thrombotic microangiopathy associated with alpha-interferon therapy for chronic myeloid leukaemia (Case Report)

SUMMARY:  The association of interferon (IFN) therapy with haemolytic uraemic syndrome in patients with chronic myeloid leukaemia (CML) has been reported infrequently. The pathogenesis of the renal lesion in such cases remains unclear. We report the case of a patient with chronic myeloid leukaemia who developed nephrotic syndrome and renal failure while being treated with hydroxyurea and IFN‐α. Renal biopsy showed features of chronic thrombotic microangiopathy. The discontinuation of IFN‐α, and a prompt institution of plasmapheresis and steroids resulted in improvement of the nephrotic syndrome and renal function. These findings suggest that long‐term IFN‐α therapy can induce thrombotic microangiopathy and haemolytic uraemic syndrome in patients with chronic myeloid leukaemia.

Thrombotic microangiopathy associated with α‐interferon therapy for chronic myeloid leukaemia (Case Report)

SUMMARY:  The association of interferon (IFN) therapy with haemolytic uraemic syndrome in patients with chronic myeloid leukaemia (CML) has been reported infrequently. The pathogenesis of the renal lesion in such cases remains unclear. We report the case of a patient with chronic myeloid leukaemia who developed nephrotic syndrome and renal failure while being treated with hydroxyurea and IFN‐α. Renal biopsy showed features of chronic thrombotic microangiopathy. The discontinuation of IFN‐α, and a prompt institution of plasmapheresis and steroids resulted in improvement of the nephrotic syndrome and renal function. These findings suggest that long‐term IFN‐α therapy can induce thrombotic microangiopathy and haemolytic uraemic syndrome in patients with chronic myeloid leukaemia.

IgM as a novel predictor of disease progression in secondary focal segmental glomerulosclerosis.

Aim To determine the role of immunoglobulin M (IgM) deposits in clinical manifestations, disease outcome, and treatment response of idiopathic and secondary focal segmental glomerulosclerosis (FSGS). Methods Kidney biopsy specimens of 171 patients diagnosed with FSGS (primary and secondary) and 50 control patients were retrospectively included in the study. For each patient, clinical and outcome data were obtained and compared to morphological parameters, including immunofluorescence analysis of mesangial IgM and complement 3 (C3) deposits analyzed on kidney biopsy samples. Results There were significant positive correlations between IgM and C3 deposition in secondary FSGS (P < 0.001) and between IgM and mesangial deposits detected by electron microscopy in secondary FSGS (P = 0.015), which indicated that higher IgM deposition correlated with higher C3 deposition and mesangial deposits only in secondary FSGS. Patients with secondary FSGS and the deposition of IgM showed inferior renal outcomes at earlier time points in comparison with patients with negative IgM expression (P = 0.022). Conclusions We detected a positive correlation between IgM and C3 in secondary FSGS. The association between IgM deposition and worse renal outcome in secondary FSGS indicates that IgM may play a role in the progression of this disease.