Association Between Membranoproliferative Glomerulonephritis and Colorectal Cancer - A Case Report.

Membranoproliferative glomerulonephritis (MPGN) is a rare glomerular disease characterized by mesangial hypercellularity and thickening of the glomerular basement membrane (GBM). MPGN can be idiopathic or associated with malignancy, systemic immune complex disorders and chronic infections. It has rarely been associated with solid organ tumors, such as lung, gastric, breast or prostate cancer. We report a patient with MPGN and coexisting colorectal carcinoma. A 48-year-old man presented with anemia, loss of weight, hypertension, and nephrotic syndrome. The renal biopsy findings were compatible with type 1 MPGN. The antineutrophilic cytoplasmic antibodies, antinuclear antibodies, anti-GBM, serologic markers of hepatitis B and hepatitis C and tumor markers were negative. After ruling out the secondary causes of MPGN, the patient was treated with pulse doses of methylprednisolone and a single dose of cyclophosphamide. However, due to the worsening anemia and rectal bleeding, a colonoscopy was performed, which established a diagnosis of adenocarcinoma of the descending colon. The patient was treated with left hemicolectomy and oral corticosteroids. Within a year after the cancer treatment, the patient experienced a complete resolution of the proteinuria and improvement of the kidney function. Although rare, MPGN can be associated with hematologic malignancies and solid organ tumors. The most common causes of secondary MPGN should be ruled out before starting specific treatment. In our patient, cancer treatment has led to a subsequent remission of the nephrotic syndrome, which indicated that this association was not coincidental but rather causal. In patients with a tumor and concomitant glomerulopathy which is suspected to be paraneoplastic in etiology, the treatment of the underlying malignancy should be prioritized.

Glomerulopathies with Fibrillary Deposits.

The glomerulopathies associated with the deposition of extracellular fibrils in the glomeruli are subdivided into Congo red positive (amyloidosis) and Congo red negative (non-amyloidotic glomerulopathies) based on Congo red staining. The non-amyloidotic glomerulopathies are divided into immunoglobulin-derived and non-immunoglobulin-derived glomerulopathies. The immunoglobulin-derived glomerulopathies: fibrillary glomerulopathy (FGn) and immunotactoid glomerulopathy (ITG) are rare glomerulopathies. The diagnosis of fibrillary-immunotactoid glomerulopathy depends on electron microscopy, which shows the presence of microfibrils in the glomeruli. The microfibrils in FGn are randomly arranged with diameters less than 30 nm. The microfibrils in ITG are larger than 30 nm with a visible lumen (microtubules), focally arranged in parallel bundles. Patients with fibrillary-immunotactoid glomerulopathy present with proteinuria (usually in the nephrotic range), microscopic hematuria, arterial hypertension, and chronic kidney disease that progresses to kidney failure over months to years. Currently, there are no guidelines for the treatment of fibrillary-immunotactoid glomerulopathy, although immunotactoid glomerulopathy could be associated with underlying hematologic disorders with the need for clone-directed therapy.

Immunotactoid Glomerulopathy: A Rare Glomerular Disease Case Study.

Immunotactoid glomerulopathy (ITG) is a rare glomerular disease with variable responsiveness to the immunosuppressive therapy and with uncertain prognosis. ITG was diagnosed in two patients with type 2 diabetes mellitus with nephrotic syndrome and chronic kidney disease. The absence of diabetic retinopathy in the first case and the recent onset of diabetes in the second case accompanied with sudden increase in the 24-hour proteinuria and rapid decline in kidney function, prompted us to perform kidney biopsy. The electron microscopy set the diagnosis of ITG in both cases. There is no consensus for the treatment of ITG. The first patient was treated with combination of steroids and mycophenolate mofetil with reduction of the 24-hour proteinuria, but with persistence of the chronic kidney disease. The second patient received high doses of steroids with continuous deterioration of kidney function with the need of hemodialysis treatment.

Markers involved in proinflammatory effects by environmental toxicants.

Toxicological studies have identified polycyclic aromatic hydrocarbons (PAH) in human breast milk, smoked and barbequed food, although the largest contribution of PAH intake into the body are cereals and cereals products. The major effects attributable to PAH appeared to occur in the liver, lungs, the hematopoietic system, and the kidney. Nevertheless, more precise mechanisms by which PAH initiates its pathological features are not fully understood. In the present study, we evaluated levels of myeloperoxidase activity, its association with nitric oxide synthesis (NO), levels of uric acid (UA) in circulating blood and glucose in female rats exposed to environmental toxicants. A higher concentration of hydrogen peroxide activates myeloperoxidase, which acts as a leucocyte attractant, contributing to enhanced iNOS activity. In parallel, uric acid in addition to its pro-inflammatory effects aggravates insulin resistance and hyperglycemia, which worsens the process. Our findings suggest potential intermediate mechanisms involved in the inflammatory effects of PAH, which might give insight for the involvement of environmental toxicants not only in carcinogenesis but also in its association with acute cardiovascular disease and induction of multi-organ damage. The development of iNOS inhibitors might be beneficial in certain inflammatory disorders.

Complications and Risks of Percutaneous Renal Biopsy.

BACKGROUND: Renal biopsy performed in native and transplant kidneys is generally considered a safe procedure. AIM: In this study, we evaluated renal biopsy complications and risk factors in one nephrology facility. MATERIAL AND METHODS: We conducted a three-year retrospective study on patients who underwent renal biopsy between January 2014 and December 2016. Strict written biopsy protocol was followed. Clinical and laboratory data were obtained from medical charts. Complications were categorised as minor and major, according to the need for intervention. Minor complications included macrohematuria and/or hematoma that did not require intervention. Major complications included hematuria or hematoma with fall of hematocrit that required a blood transfusion, surgery or caused death. A binary logistic regression model was used to analyse the possible factors associated with complications after the biopsy. RESULTS: We analysed 345 biopsies; samples were taken from patients aged from 15-81 years, of whom 61% were men. A total of 21 (6%) patients developed a complication, 4.4% minor and 1.7% major complications. There were no nephrectomy or death due to biopsy intervention. Overweight patients, as well as those with higher creatinine, lower hemoglobin, higher blood pressure and biopsy due to AKI had higher chances to develop complications (p = 0.037, p = 0.023, p = 0.032, p = 0.002, p = 0.002, respectively). The patients' age, gender, kidney dimension, number of passes and uninterrupted aspirin therapy were not found as significant predictors of complications. In the multivariate logistic model, body weight (OR = 1.031, 95%CI = 1.002-1.062), lower hemoglobin (OR = 0.973, 95%CI = 0.951-0.996) and hypertension (OR = 1.025, 95%CI = 1.007-1.044) increased the risk of complications in biopsied patients. CONCLUSION: Renal biopsy is a safe procedure with a low risk of complications when strict biopsy protocol is observed. Correction of anaemia and blood pressure is to be considered before the biopsy.

Hypomagnesemia and cause-specific mortality in hemodialysis patients: 5-year follow-up analysis.

INTRODUCTION: The aim of this prospective study was to evaluate the association between serum magnesium (Mg) and mortality, in particular the cause-specific mortality of Mg and other risk factors in hemodialysis (HD) patients. METHODS: We studied a cohort of 185 HD patients receiving thrice-weekly HD treatment, on a dialysate Mg concentration of 0.5 mmol/L. We stratified 3 patient groups according to the level of Mg: lower (<1.1 mmol/L), intermediate-reference (1.1 to <1.3 mmol/L), and higher (Mg >1.3 mm/L). RESULTS: During the 5-year follow-up, 60 patients died, with cardiovascular (CV) disease as the predominant cause (73.3%). Hazard ratio (HR) for all-cause and CV mortality were 2.55 and 2.67 in the lower versus intermediate Mg group, but there was no significant association between the higher and intermediate Mg group. Univariate Cox regression analysis showed that Mg <1.1 versus 1.1-1.30 mml/L with HR 2.34, was a significant univariate predictor for increased mortality in addition to the Hb <110 g/L, Alb <40 g/L, C-reactive protein (CRP) ≥10 mg/L and brain natriuretic peptide >1,200 pg/mL. However, in the multivariate analysis only CRP ≥10 mg/L with HR 3.89 was a significant predictor of mortality. Subgroup analyses showed that among patients with CRP >10 mg/L, HR for all-cause and CV mortality of the lower versus intermediate Mg group were 1.96 and 2.39, respectively, not reaching significance for the higher versus intermediate Mg group. Conversely, there was no association between Mg level and all-cause and CV mortality within these 3 groups among patients with CRP <10 mg/L. CONCLUSIONS: Lower serum Mg level was significantly associated with an increased all-cause and cardiovascular mortality in HD patients, especially in inflamed patients.

Cyclosporine nephrotoxicity and early posttransplant hyperkalemia in living-donor renal recipients: report of 4 cases.

OBJECTIVES: Hyperkalemia is an electrolyte disorder that may occur during the first few months after a renal transplant, in patients undergoing cyclosporine immunosuppression. We present our experience with cyclosporine-associated hyperkalemia in living-donor renal transplant recipients, with isolated clinically relevant hyperkalemia soon after surgery. MATERIALS AND METHODS: We report 4 living-donor renal recipients with hyperkalemia soon after transplant. RESULTS: Severe unexpected hyperkalemia (7.5- 9.4 mmol/L) was noted in our patients 12, 20, 22, and 34 days after transplant. The C2 cyclosporine concentration was within recommended range or slightly greater than 1200 ng/mL. The hypertonic glucose/insulin treatment along with potassium diet was without results. A reduction in daily cyclosporine dosages, along with 1- to 2-week administration of fludrocortisone was effective. The patients became normokalemic taking a standard, triple-drug immunosuppression protocol, and were discharged home with normal renal function. There were no repeat episodes of hyperkalemia in any of the patients during 12 months of follow-up. CONCLUSIONS: Cyclosporine should be considered a cause of hyperkalemia in renal transplant recipients. Successful treatment with fludrocortisone confirms that transitional pseudohypoaldosteronism has a potential nephrotoxic effect of cyclosporine. We recommend close monitoring of the cyclosporine concentration and administering fludrocortisone when treating hyperkalemia in renal transplant recipients.

The Oxford classification of IgA nephropathy: single centre experience.

The Oxford classification for the pathological classification of a glomerular disease in IgA nephropathy was established and published in 2009. Four of the pathological variables: 1) mesangial hypercellularity score, 2) segmental glomerulosclerosis, 3) endocapillary hypercellularity and 4) tubular atrophy/interstital fibrosis were presented as having value in predicting renal outcome in this glomerular disease. These features were recommended to be taken into account for predicting the outcome. In our study, we correlated these four variables with the outcome of the disease in 40 adult patients with IgA nephropathy. Standard histopathologic procedure was used to determine four variables as 0/1. The results were compared with renal outcome, clinical data were obtained from the out-patient files of the patients. The whole follow-up period was 3-27 years. The average survival of the whole group was 10.8±7.47 years (M±SD). Mesangial hypercellularity was confirmed to be associated with the renal outcome (p=0.047), as well as glomerular sclerosis (p=0.009), endocapillary hypercellularity (p=0.001) and tubular atrophy/interstitial fibrosis (p=0.045). When we analysed only patients with a severe form of the disease (nephrotic syndrome; patients treated with immunosuppression), the survival of the patients was associated only with the degree of tubulointerstitial changes (p=0.018). Analysing separately patients with mild clinical form, we found only a predictive value of segmental glomerulosclerosis on renal survival.