Vitamin C-induced oxalate nephropathy in a renal transplant patient related to excessive ingestion of cashew pseudofruit (Anacardium occidentale L.): a case report.

BACKGROUND: Ingestion of vitamin C is generally regarded as harmless. Oxalate nephropathy is an infrequent condition and is characterized by oxalate deposition in the renal tubules, in some cases resulting in acute kidney injury. It can be caused by overproduction of oxalate in genetic disorders and, more frequently, as a secondary phenomenon provoked by ingestion of oxalate or substances that can be transformed into oxalate in the patient. CASE PRESENTATION: We present a case of acute oxalate nephropathy in a 59-year-old black male with type 2 diabetes mellitus, who received a kidney transplant 11 years prior. He ingested a large amount of cashew pseudofruit ("cashew apple") during 1 month and developed acute kidney injury. His previous blood creatinine was 2.0 mg/dL, which increased to 7.2 mg/d; he required hemodialysis. He was subsequently discharged without need for dialysis; 3 months later his blood creatinine stabilized at 3.6 mg/dL. CONCLUSIONS: This pseudofruit is rich in ascorbic acid (vitamin C) and poor in oxalate. Urinary oxalate excretion begins to increase when amounts of ascorbic acid above bodily requirements are ingested, and may provoke acute oxalate nephropathy. The patient's oxalate acute nephropathy, in this case, was attributed to excessive vitamin C ingestion from the cashew pseudofruit associated with decreased renal function.

Good response of low-fat/high-protein diet in a patient with chyluria.

UNLABELLED: Chyluria is an inappropriate urinary excretion of chyle that turns the urine milky. A nutritional approach based on low-fat/high-protein content diet associated or not with medium-chain triglyceride (MCT) showed to be an efficient conservative treatment to improve the milky urine appearance in a patient with chyluria. CASE REPORT: A 30-year-old female patient was admitted with chyluria of unknown etiology. An ureteropyeloscopy revealed a single lesion in each kidney, both with linear aspect and measuring 5 mm in extension. These lesions were located close to the renal papillae and were leaking a cloudy and milky fluid. Both lesions were laser cauterized followed by improvement of the milky urine. However, the chyluria relapsed after few months and a low-fat/high-protein content diet with 10 g of soybean oil to meet the requirements essential fatty acids (EFA) and with MCT from coconut oil as alternative to prepare foods was started. Few weeks later the patient returned reporting consistent improvement of the milky urine appearance related with the use of the diet. However since the diet was tasteless and time consuming to prepare, she reported low compliance to diet with MCT and the milky urine relapsed. The MCT was discontinued and the diet with EFA source was maintained with better compliance. Since then the chyluria remains in remission. In conclusion, the dramatic improvement of the milky urine with low-fat/high-protein diet with EFA source observed in our patient demonstrates that this nutritional approach is efficient with fast results to treat chyluria during long term.

False positivity of gamma-glutamyl transpeptidase measurement in urine.

Although enzymuria tends to be associated to renal injury, there are no studies that have evaluated the presence of the enzyme gamma-glutamyl transpeptidase (GGT) spectrophotometry in the urine using a non-nephrotoxic agent (Nerium oleander) in order to evaluate the possibility of false positive results. The urinary GGT/urinary creatinine concentration ratio (uGGT/uCr) of 10 healthy dogs was calculated and posteriorly confronted with data from clinical evaluation, hematological and serum biochemical profiles, creatinine clearance (CrC), urinalysis, urine protein/creatinine ratio (UPC), electrocardiogram, systemic blood pressure (SBP) and light and electron microscopy. The results for kidney histology, SBP, UPC and CrC were not significantly different in any of the time-points analyzed. However, uGGT/uCr was significantly higher when measured 4 hours and 24 hours after administration of N. oleander. The measurement of the urinary GGT enzyme, as performed in many studies, yielded false positive results in dogs poisoned by a non-nephrotoxic agent.

Membranous glomerulonephritis associated with splenic marginal zone lymphoma mimicking multiple myeloma.

Glomerulonephritis may complicate the course of a wide variety of malignant diseases. However, there are relatively few reports of membranous glomerulonephritis (MGN) in patients with non-Hodgkin lymphoma (NHL). We describe for the first time a case of MGN associated with splenic marginal zone lymphoma with extreme plasmacytic differentiation and bone marrow infiltration mimicking multiple myeloma. We also reviewed the literature and summarize the clinical-pathological findings and the mechanisms involved in NHL-induced MGN. Our current case highlights the importance of a quick and correct diagnosis of the underlying disease and the value of a thorough physical examination. Clinicians should be aware of the possibility of an underlying hematologic malignancy in such cases, particularly in elderly patients with renal biopsy that shows the presence of atypical histology.

What lies beneath: Fabry nephropathy in a female patient with severe cerebrovascular disease.

Fabry disease is an X-linked inborn error of metabolism, which is caused by the deficiency of α-galactosidase A, leading to progressive accumulation of neutral glycosphingolipids and a-galactosyl breakdown products in most body fluids and several tissues, resulting in the clinical manifestations. The onset of Fabry disease symptoms in females is not observed as early as in males. We report a novel presentation of Fabry disease in a female patient with medical history of relapsing strokes and brain magnetic resonance angiography showing signs of microangiopathy and multiple lacunar strokes that were first diagnosed as Moyamoya disease (a chronic progressive cerebrovascular disease). The patient subsequently displayed increased levels of serum creatinine and proteinuria. Diagnosis of Fabry disease was made by a renal biopsy and was confirmed by molecular studies showing a missense mutation: c1066C > T (het) [R356W]. The diagnosis was delayed by 21 years with respect to her first symptom (stroke), probably because her initial clinical presentation was neurological and diagnosed as Moyamoya disease. Other factors that contributed to the delay of the diagnosis were the lack of acute or chronic pain (neuropathic pain) and angiokeratomas. Some similarities in the pathogenic aspects of the patient's vascular lesions lead us to speculate that this patient has Fabry disease, with a phenotype that had not yet been described. It is necessary to be aware of this possibility to avoid misdiagnosis of Fabry disease as Moyamoya disease.

Elucidating the neurotoxicity of the star fruit.

Caramboxin: Patients suffering from chronic kidney disease are frequently intoxicated after ingesting star fruit. The main symptoms of this intoxication are named in the picture. Bioguided chemical procedures resulted in the discovery of caramboxin, which is a phenylalanine-like molecule that is responsible for intoxication. Functional experiments in vivo and in vitro point towards the glutamatergic ionotropic molecular actions of caramboxin, which explains its convulsant and neurodegenerative properties.

Membranous nephropathy.

Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.

Renal involvement in systemic lupus erythematosus: additional histopathological lesions.

A common criticism of the classification of lupus nephritis is the relative scarcity of information regarding tubular, interstitial, and vascular changes compared to the available information regarding glomerular changes, even though their potential for independent progression is known. This study reviewed the importance of less explored lesions by the current and widely used 2003 classification of lupus nephritis of the International Society of Nephrology/Renal Pathology Society (ISN/RPS), with emphasis on the tubulointerstitial, podocyte, and vascular lesions, increasingly recognised as being important in the pathogenesis and prognosis of the disease. Recognition of these lesions can help with therapeutic decision-making, thereby allowing better results for patients with systemic lupus erythematosus.

Endophthalmitis: a rare but devastating metastatic bacterial complication of hemodialysis catheter-related sepsis.

There are many infectious complications related to vascular access in patients undergoing maintenance hemodialysis. We report two cases of endophthalmitis as a metastatic infection associated with a tunneled catheter and a temporary dual lumen catheter. Both patients were diabetic. A 61-year-old female on maintenance hemodialysis by a jugular tunnelized catheter during the past year was receiving parenteral antibiotics for catheter salvage due to fever episodes in the last 3 months. She was admitted to the hospital presenting pain, proptosis, conjunctival hyperemia, corneal infiltrate, and visual acuity of no light perception (NLP). A 51-year-old male recently undergoing hemodialysis by a temporary dual lumen catheter presented fever. His catheter was removed, but he was admitted to the hospital presenting fever, decreased vision, edema, and pain in his left eye. On examination, eyelid edema, conjunctival hyperemia, purulent secretion, hypopyon in the pupils, and visual acuity of NLP were verified. A diagnosis of endogenous endophthalmitis was made in both patients on clinical grounds and computed tomography. Evisceration of the left eye was the first option of treatment for both patients due to poor vision. Cultures of the eviscerated ocular globes showed Staphylococcus hemolyticus and Staphylococcus aureus, respectively. After evisceration, both patients received treatment, had a good outcome, and were discharged to continue their hemodialysis program. Metastatic bacterial endophthalmitis is a rare complication of dialysis catheter-related bacteremia. When suspected, urgent ophthalmologic evaluation and treatment are needed to reduce the risk of losing vision in the affected eye.

Lipoprotein glomerulopathy associated with the Osaka/Kurashiki APOE variant: two cases identified in Latin America.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant disease caused by mutations in APOE, the gene which encodes apolipoprotein E. LPG mainly affects Asian individuals, however occasional cases have also been described in Americans and Europeans. Herein we report two unrelated Brazilian patients with LPG in whom genetic analyses revealed the APOE-Osaka/Kurashiki variant. CASE PRESENTATION - CASE 1: A 29-year-old Caucasian male sought medical attention with complaints of face swelling and foamy urine for the last 3 months. He denied a family history of kidney disease, consanguinity, or Asian ancestry. His tests showed proteinuria of 12.5 g/24 h, hematuria, serum creatinine 0.94 mg/dL, albumin 2.3 g/dl, total cholesterol 284 mg/dL, LDL 200 mg/dL, triglycerides 175 mg/dL, and negative screening for secondary causes of glomerulopathy. A kidney biopsy revealed intraluminal, laminated deposits of hyaline material in glomerular capillaries consistent with lipoprotein thrombi. These findings were confirmed by electron microscopy, establishing the diagnosis of LPG. His apolipoprotein E serum level was 72 mg/dL and genetic analysis revealed the APOE pathogenic variant c.527G > C, p.Arg176Pro in heterozygosis, known as the Osaka/Kurashiki mutation and positioned nearby the LDL receptor binding site. CASE 2: A 34-year-old Caucasian man sought medical assessment for renal dysfunction and hypertension. He reported intermittent episodes of lower-limb edema for 3 years and a family history of kidney disease, but denied Asian ancestry. Laboratorial tests showed BUN 99 mg/dL, creatinine 10.7 mg/dL, total cholesterol 155 mg/dL, LDL 79 mg/dL, triglycerides 277 mg/dL, albumin 3.1 g/dL, proteinuria 2.7 g/24 h, and negative screening for secondary causes of glomerulopathy. His kidney biopsy was consistent with advanced chronic nephropathy secondary to LPG. A genetic analysis also revealed the Osaka/Kurashiki variant. He was transplanted a year ago, displaying no signs of disease relapse. CONCLUSION: We report two unrelated cases of Brazilian patients with a diagnosis of lipoprotein glomerulopathy whose genetic assessment identified the APOE-Osaka/Kurashiki pathogenic variant, previously only described in eastern Asians. While this is the second report of LPG in Latin America, the identification of two unrelated cases by our medical team raises the possibility that LPG may be less rare in this part of the world than currently thought, and should definitely be considered when nephrotic syndrome is associated with suggestive kidney biopsy findings.

Evaluation of erythrocyte dysmorphism by light microscopy with lowering of the condenser lens: A simple and efficient method.

AIM: To demonstrate that the evaluation of erythrocyte dysmorphism by light microscopy with lowering of the condenser lens (LMLC) is useful to identify patients with a haematuria of glomerular or non-glomerular origin. METHODS: A comparative double-blind study between phase contrast microscopy (PCM) and LMLC is reported to evaluate the efficacy of these techniques. Urine samples of 39 patients followed up for 9 months were analyzed, and classified as glomerular and non-glomerular haematuria. The different microscopic techniques were compared using receiver-operator curve (ROC) analysis and area under curve (AUC). Reproducibility was assessed by coefficient of variation (CV). RESULTS: Specific cut-offs were set for each method according to their best rate of specificity and sensitivity as follows: 30% for phase contrast microscopy and 40% for standard LMLC, reaching in the first method the rate of 95% and 100% of sensitivity and specificity, respectively, and in the second method the rate of 90% and 100% of sensitivity and specificity, respectively. In ROC analysis, AUC for PCM was 0.99 and AUC for LMLC was 0.96. The CV was very similar in glomerular haematuria group for PCM (35%) and LMLC (35.3%). CONCLUSION: LMLC proved to be effective in contributing to the direction of investigation of haematuria, toward the nephrological or urological side. This method can substitute PCM when this equipment is not available.

The Prevalence of Nondiabetic Renal Diseases in Patients with Diabetes Mellitus in the University Hospital of Ribeirão Preto, São Paulo.

OBJECTIVE: To evaluate the prevalence of nondiabetic renal diseases (NDRDs) in renal biopsies of patients with diabetes mellitus (DM) in the University Hospital of Ribeirão Preto, São Paulo. Research Design and Methods. We conducted a retrospective study including kidney biopsies performed in diabetic patients between 1987 and 2013. We evaluated 79 biopsies during this period. The primary variable was the prevalence of NDRD in patients with DM. The secondary variables were the presence of systemic arterial hypertension (SAH), hematuria, time since diagnosis of DM, serum creatinine, and proteinuria levels. The cases were divided into the following groups: isolated diabetic nephropathy (DN-group I), isolated nondiabetic renal diseases (NDRD-group II), associated NDRD/DN (group III), and associated NDRD+NDRD/DN (group IV). RESULTS: Most of the patients (58.22%) presented only alterations arising from DN. NDRDs were present in 41.77% of the patients. Membranous glomerulonephritis (30.3%) and IgA nephropathy (24.24%) were the most prevalent NDRDs. We found no differences between female and male patients with NDRD when assessing the secondary variables. A time since diagnosis of five years or less revealed a statistical difference (p = 0.0005) in the comparison between the isolated DN (group I) and the NDRD+NDRD/DN (group IV). The other secondary variables were not significant in the comparison of the groups. CONCLUSIONS: We concluded that the prevalence of NDRD is 41.77%. Membranous glomerulonephritis was the most prevalent NDRD in our study. We also conclude that the probability of the presence of NDRD with or without concomitant DN is greater for patients who had biopsies with a time since diagnosis of five years or less. A time since diagnosis of ten years or more does not allow the exclusion of the presence of NDRD.

Effect of Lercanidipine on the Pharmacokinetics-Pharmacodynamics of Carvedilol Enantiomers in Patients With Chronic Kidney Disease.

This study evaluates the carvedilol-lercanidipine drug interaction, and the influence of chronic kidney disease (CKD) on both drugs. Patients with high blood pressure (8 with normal renal function [control] and 8 with CKD with estimated glomerular filtration rate categories of G3b to G5 [12-38 mL/min/1.73 m2 ]) were included and prescribed 3 different treatment regimens, a single oral dose of racemic carvedilol 25 mg (CAR), a single oral dose of racemic lercanidipine 20 mg (LER), and single oral doses of CAR plus LER. Blood samples were collected and variations in heart rate were assessed (using isometric exercise with handgrip) for up to 32 hours. Lercanidipine pharmacokinetics were not enantioselective, and were not affected by carvedilol and CKD. Carvedilol pharmacokinetics (data presented as median) were enantioselective with higher plasma exposure of (R)-(+)-carvedilol in both control (103.5 vs 46.0 ng ∙ h/mL) and CKD (190.6 vs 98.9 ng ∙ h/mL) groups. Lercanidipine increased the area under the plasma concentration-time curve of only (R)-(+)-carvedilol in the CKD group (190.6 vs 242.2 ng ∙ h/mL) but not in the control group (103.5 vs 98.7 ng ∙ h/mL). CKD increased plasma exposure (46.0 vs 98.9 ng ∙ h/mL) and effect-compartment exposure (5.5 vs 20.9 ng ∙ h/mL) to (S)-(-)-carvedilol, resulting in higher ß-adrenergic inhibition (10.0 vs 6.1 bpm). Therefore, carvedilol dose titration in CKD patients with estimated glomerular filtration rate categories of G3b to G5 should be initiated, with no more than half the dose used for patients with normal renal function.

Influence of glomerular filtration rate on the pharmacokinetics of cyclophosphamide enantiomers in patients with lupus nephritis.

The pharmacokinetics of cyclophosphamide (CYC) enantiomers were evaluated in patients with lupus nephritis distributed in 2 groups according to creatinine clearance: group 1 (90.6-144.6 mL/min/1.73 m(2)) and group 2 (42.8-76.4 mL/min/1.73 m(2)). All patients were treated with 0.75 to 1.3 g of racemic CYC as a 2-hour infusion and with 1 mg intravenous midazolam as a drug-metabolizing marker. CYC enantiomers and midazolam concentrations in plasma were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS). The following differences (Wilcoxon test, P < or = .05) were observed between the (S)-(-) and (R)-(+) enantiomers: AUC(0-infinity) 152.41 vs 129.25 microg.h/mL, CL 3.28 vs 3.89 L/h, Vd 31.38 vs 29.74 L, and t((1/2)) 6.79 vs 5.56 h for group 1 and AUC(0-infinity) 167.20 vs 139.08 microg.h/mL, CL 2.99 vs 3.59 L/h, and t((1/2)) 6.15 vs 4.99 h for group 2. No differences (Mann test, P < or = .05) were observed between groups 1 and 2 in the pharmacokinetic parameters of both enantiomers. No significant relationship was observed between midazolam clearance (2.92-16.40 mL/min.kg) and clearance of each CYC enantiomer. In conclusion, CYC kinetic disposition is enantioselective, resulting in higher exposures of the (S)-(-) enantiomer in lupus nephritis patients, and the pharmacokinetic parameters of both enantiomers are not altered by the worsening of renal condition.

Effect of the absence of interleukin-12 on mesangial proliferative glomerulonephritis induced by habu snake venom.

BACKGROUND: Interleukin-12 (IL12) participates in the pathophysiology of various experimental types of progressive glomerulonephritis, but its role in acute mesangial glomerulonephritis (AMG) induced by habu snake venom (HSV) has not been determined. This study aims to evaluate the effect of the absence of IL12 on AMG induced by HSV. METHODS: AMG was induced in IL12 knockout (IL12-/-) and C57Bl/6 (IL12+/+) mice by a single i.v. administration of HSV. Vehicle was used in control animals. Mice were studied after 3, 7, and 14 days (D3, D7, and D14). RESULTS: After treatment with HSV, IL12+/+ and -/- mice developed focal glomerular lesions, but groups of both lineages showed no statistical difference concerning albuminuria, serum creatinine, histopathology, number of cells by glomerular tuft, and glomerular tuft area. Compared to IL12+/+ mice, IL12-/- mice showed lower scores of glomerular desmin expression on D7 [1.55 (1.32; 1.65) vs. 1.12 (1.07; 1.22); p < 0.01] and D14 [1.60 (1.55; 1.75) vs. 1.20 (1.15; 1.20); p < 0.001], respectively, and lower scores of glomerular alpha-SMA expression on D14 [0.30 (0.21; 0.38) vs. 0.16 (0.26; 0.36); p < 0.001], respectively. CONCLUSION: The absence of IL12 reduced the activity of mesangial cells, but did not modify the course of HSV-induced AMG in mice.

Cytomegalovirus infection in kidney allografts: a review of literature.

Cytomegalovirus (CMV) is an important cause of renal transplantation complications. It can cause different syndromes or end-organ diseases that can lead to unfavourable clinical outcomes and kidney allograft dysfunction. Although well documented as a systemic disease on renal transplant patients, affecting non-renal tissue, as gastrointestinal and respiratory tract, few cases have been reported in English-language indexed journals involving renal allograft lesions secondary to CMV. As an important differential diagnosis and etiological agent to acute and chronic rejection, the possibility of CMV kidney direct infection needs prompt recognition for effective treatment. In this paper, we will review the current literature about CMV nephritis and discuss the findings from each case report.

Membranous nephropathy / Nefropatia membranosa

ABSTRACT Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.

RESUMO A nefropatia membranosa é uma glomerulopatia, cujo principal alvo acometido é o podócito, e acarreta consequências na membrana basal glomerular. Tem maior frequência em adultos, principalmente acima dos 50 anos. A apresentação clínica é a síndrome nefrótica, mas muitos casos podem evoluir com proteinúria não nefrótica assintomática. O mecanismo consiste na deposição de complexos imunes no espaço subepitelial da alça capilar glomerular com subsequente ativação do sistema do complemento. Grandes avanços na identificação de potenciais antígenos alvo têm ocorrido nos últimos vinte anos, e o principal é a proteína "M-type phospholipase-A2 receptor" (PLA2R) com o anticorpo anti-PLA2R circulante, o que possibilita avaliar a atividade e o prognóstico dessa nefropatia. Essa via de lesão corresponde aproximadamente a 70% a 80% dos casos da nefropatia membranosa caracterizada como primária. Nos últimos 10 anos vários outros antígenos alvo potenciais têm sido identificados. Esta revisão se propõe a apresentar de modo didático aspectos clínicos, etiopatogênicos e terapêuticos da nefropatia membranosa, incluídos os casos com ocorrência no transplante renal.

Urinary excretion of monocyte chemoattractant protein-1: a biomarker of active tubulointerstitial damage in patients with glomerulopathies.

BACKGROUND/AIMS: The urinary concentration of the monocyte chemoattractant protein-1 (uMCP-1) chemokine is increased in several proteinuric and/or inflammatory renal diseases. In the present study, we evaluated the association between uMCP-1 and renal function, proteinuria, glomerular and interstitial macrophage infiltration, and renal fibrosis in patients with primary and secondary glomerulopathies diagnosed by renal biopsy. METHODS: Thirty-seven patients aged 32.6 +/- 7.7 years were studied. uMCP-1 was determined by ELISA. Renal macrophage expression (CD68 positive cells) is reported as number of macrophages/10(4) microm2 of the cortical tubulointerstitial (TI) area or of glomerular capillary tuft area. Cortical interstitial fibrosis was quantitated by PicroSirius red staining under polarized light by a computerized manner. RESULTS: The uMCP-1 ratio (pg/ml/urinary creatinine mg/ml) was positively correlated (Spearman coefficient) with proteinuria (r = 0.4629; p < 0.005) and number of macrophages in the cortical TI area (r = 0.64; p = 0.0005), and negatively correlated with creatinine clearance (r = -0.4877; p < 0.001). The uMCP-1 ratio was not significantly correlated with number of macrophages/glomerular capillary tuft area (r = 0.27; p = 0.19) or with percent cortical interstitial fibrosis (r = 0.08; p = 0.62). CONCLUSIONS: The uMCP-1 excretion is a biomarker of the inflammatory activity of the TI area, and does not reflect chronic interstitial damage.