Isolated massive histiocytes renal interstitial infiltration: a case report of an unexpected cause of acute kidney injury in a kidney transplant recipient.

BACKGROUND: Acute kidney injury is a frequent cause of hospital readmission in kidney transplant recipients (KTR), usually associated with infections and graft rejection. Herein, we report a case of an unusual cause of acute kidney injury in a KTR (massive histiocytes renal interstitial infiltration). CASE PRESENTATION: A 40-year-old woman was submitted to a second kidney transplant. One year after surgery, she presented asthenia, myalgia, and fever, haemoglobin 6.1 g/dL; neutrophils: 1.3 × 109/µL; platelets: 143 × 109/µL; blood creatinine 11.8 mg/dL, requiring dialysis. A kidney biopsy revealed diffuse histiocytic infiltration, which was assumed due to dysregulated immunological activation triggered by infections. The patient had multiple infections, including cytomegalovirus infection (CMV), aspergillosis, bacteraemia, and urinary tract infections, which could trigger the immune response. Haemophagocytic lymphohistiocytosis (HLH) was ruled out. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies. CONCLUSIONS: Renal histiocyte activation and infiltration may have been initiated by an immunological mechanism similar to what occurs in HLH and infectious processes. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies.

Calcitriol Reduces the Inflammation, Endothelial Damage and Oxidative Stress in AKI Caused by Cisplatin.

Cisplatin treatment is one of the most commonly used treatments for patients with cancer. However, thirty percent of patients treated with cisplatin develop acute kidney injury (AKI). Several studies have demonstrated the effect of bioactive vitamin D or calcitriol on the inflammatory process and endothelial injury, essential events that contribute to changes in renal function and structure caused by cisplatin (CP). This study explored the effects of calcitriol administration on proximal tubular injury, oxidative stress, inflammation and vascular injury observed in CP-induced AKI. Male Wistar Hannover rats were pretreated with calcitriol (6 ng/day) or vehicle (0.9% NaCl). The treatment started two weeks before i.p. administration of CP or saline and was maintained for another five days after the injections. On the fifth day after the injections, urine, plasma and renal tissue samples were collected to evaluate renal function and structure. The animals of the CP group had increased plasma levels of creatinine and of fractional sodium excretion and decreased glomerular filtration rates. These changes were associated with intense tubular injury, endothelial damage, reductions in antioxidant enzymes and an inflammatory process observed in the renal outer medulla of the animals from this group. These changes were attenuated by treatment with calcitriol, which reduced the inflammation and increased the expression of vascular regeneration markers and antioxidant enzymes.

Effects of previous physical training on adriamycin nephropathy and its relationship with endothelial lesions and angiogenesis in the renal cortex.

AIMS: Adriamycin (ADR)-induced nephropathy is one of the most experimental models used in progressive kidney disease. A single dose of this drug induces a progressive and irreversible proteinuria that progresses to focal segmental glomerulosclerosis and tubulointerstitial lesions. Regular physical activity has been considered as a therapeutic intervention in several diseases. This study evaluated the influence of previous physical training in renal damage induced by ADR and the role of endothelial lesions and angiogenesis in this process. MAIN METHODS: Male Wistar rats were subjected or not to treadmill running for 4weeks and then injected with ADR (2.5mg/kg, i.v.) or saline. Twenty-four-hour urine samples were collected for albuminuria measurement, and blood samples were collected to measure plasma creatinine 60days after the injections. The kidneys were removed for histological, immunohistochemical, Western blot and ELISA studies. KEY FINDINGS: ADR-treated rats presented increases in plasma creatinine levels, albuminuria, podocyte damage, and enlargement of the tubular interstitial relative area, as well as higher macrophage numbers in the renal cortex, interleukin (IL)-1ß levels in renal tissue and urinary monocyte chemoattractant protein (MCP)-1, which were associated with reduction in vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS) expressions and peritubular capillary (PTC) density in renal cortex. These alterations were less intense in the animals subjected to previous exercise training. SIGNIFICANCE: Physical training prior to ADR injection reduced the renal damage induced by this drug. This effect was related to angiogenesis and reduction in the endothelial lesions and inflammatory process in the renal cortex of these animals.

Gleason score and tumor laterality in radical prostatectomy and transrectal ultrasound-guided biopsy of the prostate: a comparative study.

We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate (TRUSBX) and radical prostatectomy (RP). Some factors that could cause a discrepancy in results between these two procedures were also evaluated. Among the 318 cases reviewed, 191 cases were selected for inclusion in this comparative study. We divided the patients into two groups using the Gleason score: an intermediate/high-grade group (≥7) and a low-grade group (<6). Exploratory analyses were conducted for comparisons between groups. We also performed comparisons between TRUSBX and RP for tumor laterality. TRUSBX overestimated 6% and underestimated 24% cases in comparison with RP for Gleason score, and overestimated 2.6% and underestimated 46% cases compared with RP for tumor laterality. Biopsy specimens were slightly smaller in TRUSBX cases with underestimated tumor laterality (P < 0.05), and no relationship between the biopsy specimen size and underestimated Gleason score in TRUSBX was found. Prostatic volume showed no statistical correlation with the likelihood of under or overestimation (P > 0.05). Thus, our study showed that TRUSBX has a high likelihood of underestimating both the Gleason score and tumor laterality in prostate cancer (PCa). The size of the fragment appears to be an important factor influencing the likelihood of laterality underestimation and Gleason score overestimation via TRUSBX. Due to the high likelihood of underestimation of the Gleason score and tumor laterality by 12-core prostate biopsy, we conclude that this type of biopsy should not be used alone to guide therapy in PCa.

A novel case report of sickle cell disease-associated immunoglobulin A nephropathy: the diagnostic value of erythrocyte dysmorphism evaluation.

Sickle cell disease is a severe disease with a genetic pattern; it may cause anemia, vaso-occlusive phenomena, and multiorgan injury. It may damage any renal compartment, thereby causing tubular abnormalities, papillary necrosis, or glomerulopathies such as focal and segmental glomerulosclerosis and membranoproliferative pattern. The clinical consequences are hematuria and proteinuria. Hematuria associated with SCD is characteristically isomorphic (non-glomerular). This case report describes a novel case of a patient with sickle cell disease who presented with proteinuria and microscopic dysmorphic (glomerular) hematuria. A renal biopsy revealed immunoglobulin A nephropathy. Despite the fact that immunoglobulin A nephropathy is the most commonly diagnosed glomerulonephritis worldwide, an association between this entity and sickle cell disease has not yet been reported, probably because all cases of hematuria in patients with sickle cell disease have been regarded as secondary to sickle cell disease. Thus, new approaches are necessary to differentiate these conditions, such as evaluation of urinary erythrocyte dysmorphism, even more so because these two entities have different therapeutic options, morbidity, and mortality rates.

Brazilian embauba (Cecropia pachystachya) extract reduces renal lesions in 5/6 nephrectomized rats.

INTRODUCTION: Cecropia pachystachya (CP) is a plant rich in polyphenols which inhibits the angiotensin-converting enzyme (ACE) in vitro. Angiotensin II (AII) has an important role in the renal lesion provoked by 5/6 nephrectomy (NE). This study evaluated the CP extract effect on renal lesions provoked by 5/6 NE. MATERIALS AND METHODS: Male Wistar rats submitted to 5/6 NE were treated or not treated with CP extract and followed for 90 days. Systemic blood pressure (SBP), albuminuria, renal functional and structural parameters, ACE activity, urinary levels of monocyte chemoattrant protein-1 (MCP-1) and transforming growth factor ß (TGF-ß) were evaluated. RESULTS: Albuminuria and hypertension were less intense in the treated (NE+CP) group compared to the untreated (NE) group. CP extract treatment reduced the fall in glomerular filtration rate observed in NE rats. Glomerulosclerosis, tubulointerstitial lesions, increase of macrophages and AII positive cells in the renal cortex, as well as increases in renal ACE activity, urinary levels of MCP-1 and TGF-ß were attenuated in NE rats by CP treatment. CONCLUSIONS: The treatment with CP extract reduced the SBP and functional and structural renal changes in 5/6 NE rats. These effects were associated with decreased AII expression, ACE activity and inflammation in the renal cortex.

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.

Minimal change disease associated with type 1 and type 2 diabetes mellitus.

A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents.

Minimal change disease associated with type 1 and type 2 diabetes mellitus / Glomerulopatia de lesões mínimas associada ao diabetes melito do tipo 1 e do tipo 2

A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents.

Uma paciente de 19 anos de idade com diabetes tipo 1 durante quatro anos e uma paciente de 73 anos de idade com diabetes tipo 2 durante vinte anos desenvolveram quadro súbito de síndrome nefrótica. O exame histológico à microscopia de luz, imunofluorescência e microscopia eletrônica (em um caso) diagnosticou glomerulopatia de lesões mínimas (GLM) em ambos os casos. Na paciente de 73 anos de idade, houve uma associação com o uso de meloxicam. As duas pacientes foram tratadas com corticosteroides e responderam com remissão completa do quadro. A paciente de 19 anos com diabetes tipo 1 apresentou remissão completa sem recidivas, e a paciente de 73 anos com diabetes tipo 2 apresentou dois episódios de recidiva; a remissão completa foi conseguida após associação ao tratamento com ciclofosfamida. As duas pacientes foram seguidas dois anos após a remissão completa. Os casos descritos enfatizam o papel da biópsia renal em pacientes diabéticos com evolução atípica do aparecimento de proteinúria, pois pacientes com GLM respondem bem à corticoterapia como único tratamento ou associado a outro agente imunossupressor.

Minimal change disease: a variant of lupus nephritis.

Some patients with systemic lupus erythematosus (SLE) present with nephrotic syndrome due to minimal change disease (MCD). Histopathological diagnosis of patients with SLE and nephrotic-range proteinuria has shown that these patients present with diffuse proliferative glomerulonephritis and membranous glomerulonephritis, World Health Organization (WHO) classes IV and V, respectively, more frequently than the other classes. In the present study, we reported a case of nephrotic syndrome and renal biopsy-proven MCD associated with SLE. A complete remission occurred after steroid treatment, which was followed by a relapse 15 months later with a concomitant reactivation of SLE. A second biopsy showed WHO class IIb lupus nephritis. Prednisone treatment was restarted, and the patient went into complete remission again. The association of MCD and SLE may not be a coincidence, and MCD should be considered as an associated SLE nephropathy.

Treatment with a p38 MAPK inhibitor attenuates cisplatin nephrotoxicity starting after the beginning of renal damage.

AIMS: Cisplatin (CP) promotes increased production of reactive oxygen species, which can activate p38 mitogen activated protein kinases (p38 MAPKs) leading to apoptosis and increased expression of proinflammatory mediators that intensify the cytotoxic effects of CP. We investigated the effect of the treatment with SB203580, a p38 MAPKs inhibitor, on oxidative stress, on the oxidation-associated signal, p38 MAPK and on apoptosis in CP-injected rats, starting after the beginning of the renal damage. MAIN METHODS: Rats (n = 21) were injected with CP (5 mg/kg, i.p.) and 3 and 4 days after some of them (n = 8) were treated with SB203580 (0.5 mg/kg, i.p.). Controls (n = 6) received saline (i.p.). Two or five days after saline or CP injections, plasma creatinine, urinary volume, sodium and potassium fractional excretions, blood urea nitrogen and urinary lipid peroxidation were measured. The kidneys were removed for histological, apoptosis, immunohistochemical and Western blot studies. KEY FINDINGS: CP caused abnormalities in kidney functions and structure associated with raised urinary peroxidation levels and higher number of apoptotic cells in the outer medulla. The immunostaining studies showed increased numbers of macrophages/monocytes and p-p38 MAPKs positive cells in the renal outer medulla. The increase of p-p38 MAPKs expression was confirmed by Western blot analysis. All of these alterations were attenuated by treatment with SB203580. SIGNIFICANCE: These data suggest that the beneficial effect of SB203580 on CP-induced renal damage might be related, in part, to the blockade of p38 MAPK activation with reduction of the inflammatory process, oxidative stress and apoptotic cell death.

Effects of resveratrol on glycerol-induced renal injury.

Glycerol-induced renal lesions can have many causes, including increased oxidative stress and inflammation. Resveratrol, a polyphenolic phytoalexin found in grapes and red wine, is an antioxidant agent with anti-inflammatory effects. In the present study, we investigated the possible protective effect of resveratrol on glycerol-induced nephrotoxicity. Male Wistar rats were injected intramuscularly with 8 ml/kg of either 50% glycerol (n=18), glycerol+resveratrol (n=22), 0.15 M saline (n=14), saline+carboxymethylcellulose (n=10) or saline+resveratrol (n=8). The rats were killed 3 days after the injections, at which time the kidneys were removed for histological and immunohistochemical studies and lipid peroxidation determination. Blood and urine samples were collected in order to quantify sodium and creatinine. The results of the histological and immunohistochemical studies were scored according to the extent of damage and immunostaining, respectively, in the cortical tubulointerstitium. Lipid peroxidation was estimated by measuring malondialdehyde in renal tissue samples collected from control rats and glycerol-injected rats. By postinjection day 3, glycerol-only treated rats presented increases in plasma creatinine levels, as well as in fractional excretion of sodium and potassium (P<0.001). These increases were less pronounced in glycerol+resveratrol-treated rats (P<0.05). Cortical expression of macrophages, lymphocytes, nuclear factor-kappa B, heme oxygenase-1 and nitrotyrosine was greater in glycerol-treated rats than in controls (P<0.001). In addition, the histological findings for glycerol-treated rats were characteristic of acute tubular necrosis. Resveratrol attenuated all of these alterations (P<0.001). We conclude that resveratrol ameliorates glycerol-induced renal injury by suppressing the inflammatory process and by inhibiting lipid peroxidation.

ATP-sensitive potassium channel blockage attenuates cisplatin-induced renal damage.

BACKGROUND: Cisplatin-induced renal damage was associated with an inflammatory process. ATP-sensitive potassium channels can be involved in neutrophil migration. This study evaluated the effects of glibenclamide, an ATP-sensitive potassium channel blocker, on cisplatin-induced renal damage. METHODS: A total of 48 Wistar rats received glibenclamide (20 mg/kg/day, s.c.) and 24 h later, these animals, and an additional group of 45 rats, were injected with cisplatin (5 mg/kg, i.p.). In addition, 38 control rats were injected with saline, i.p. Twenty-four hours and 5 days after saline or cisplatin injections blood and urine samples were collected to evaluate renal function and the kidneys were removed for analysis of neutrophil accumulation, tumor necrosis factor-alpha and interleukin-1beta and histological and immunohistochemical studies. RESULTS: Cisplatin injection induced neutrophil recruitment and increased tumor necrosis factor-alpha and interleukin-1beta contents in renal cortices and outer medullae tissues. Cisplatin-treated rats also presented reduction in the glomerular filtration rate, as well as greater immunostaining for ED1 (macrophages/monocytes) and acute tubular necrosis. All of these alterations were reduced by treatment with glibenclamide. These effects seem to be related, at least in part, to the restriction of neutrophil recruitment and inflammatory process observed in the kidneys from glibenclamide+cisplatin-treated rats.

Effect of JNK inhibition on cisplatin-induced renal damage.

BACKGROUND: Cisplatin therapy is effective against many tumours, however, the nephrotoxicity of this drug is a dose-limiting factor. Apoptosis and necrosis of tubular cells and inflammatory events contribute to the cisplatin-induced nephrotoxicity. Cisplatin promotes increased production of reactive oxygen species, which can activate c-jun N-terminal kinase (JNK) that is a mediator of apoptosis and can lead to increased expression of proinflammatory mediators that could intensify the cytotoxic effects of cisplatin. In this study, we evaluated the effect that SP600125, a selective inhibitor of phosphorylated JNK (p-JNK), has on the renal damage caused by cisplatin use. METHODS: A total of 33 male Wistar rats received SP600125 (15 mg/kg/day, s.c., diluted in polyethylene glycol) for 4 days. At 24 h after the first dose, those 33 rats, plus an additional 30, were injected with cisplatin (5 mg/kg, i.p.). In addition, 18 control rats were injected with saline, and 12 rats with polyethylene glycol. At 2 and 5 days after saline or cisplatin injection, blood and urine samples were collected for measurement of creatinine, sodium and potassium, and the kidneys removed for histological, immunohistochemical and Western blot studies. RESULTS: Cisplatin-treated rats presented higher plasma creatinine, as well as greater immunostaining for ED1 (macrophages/monocytes), p-JNK, apoptotic cells, and tubular cell necrosis in the renal cortices and outer medullae. The increase of p-JNK expression was also confirmed by Western blot analysis. All of these alterations were attenuated by treatment with SP600125. CONCLUSION: The protective effect of SP600125 on cisplatin-induced renal damage seems to be related to the reduction in the apoptotic cell death and to the restriction of renal inflammation.

Parthenolide reduces cisplatin-induced renal damage.

Inflammatory events contribute to cisplatin-induced renal damage. Cisplatin promotes increased production of reactive oxygen species, which can activate nuclear factor-kappaB (NF-kappaB) that lead to increased expression of proinflammatory mediators which could intensify the cytotoxic effects of cisplatin. In this study, we evaluated the effect of parthenolide, a selective inhibitor of NF-kappaB, on renal damage caused by cisplatin use. A total of 94 male Wistar rats were divided into six groups: Group A (18 rats) were treated with saline; Group B (12 rats) received dimethylsulfoxide plus saline (the solvent for parthenolide); Group C (12 rats) received parthenolide (3mg/kg) plus saline; Group D (20 rats) received cisplatin (5mg/kg, i.p.); Group E (12 rats) received dimethylsulfoxide plus cisplatin (5mg/kg, i.p.); and Group F (21 rats) received parthenolide (3mg/kg) plus cisplatin (5mg/kg, i.p.). Dimethylsulfoxide or parthenolide were administered at 24h and 1h prior to cisplatin injection, and again at 24h and 48h after. At 2, 3 and 5 days after saline or cisplatin injection, blood and urine samples were collected for measurement of creatinine, sodium and potassium and the kidneys removed for histological, morphometric, electrophoretic mobility shift assay (EMSA), apoptosis and immunohistochemical studies. Cisplatin-treated rats presented higher plasma creatinine, as well as greater immunostaining for ED1 (macrophages/monocytes) and NF-kappaB in the renal cortices and outer medullae. The increase of NF-kappaB activation was confirmed by EMSA. Cisplatin-injected rats also presented higher urinary levels of lipid peroxidation and acute tubular necrosis. All of these alterations were reduced by treatment with parthenolide. This effect seems to be related, at least in part, to the restriction of renal inflammatory process observed in parthenolide+cisplatin treated rats.

Comparative study of multiple dosage of quercetin against cisplatin-induced nephrotoxicity and oxidative stress in rat kidneys.

Quercetin, a typical bioflavonoid ubiquitously present in fruits and vegetables, is considered to be helpful for human health. Cisplatin (cDDP) is one of the most active cytotoxic agents in the treatment of a wide range of solid tumors. The aim of this study was to investigate the possible effect of quercetin, a bioflavonoid with antioxidant potential, on cisplatin-induced nephrotoxicity and lipid peroxidation in rats. Gavage administrations of water, propylene glycol and quercetin (50 mg/kg) were made 24 and 1 h before saline or cDDP (5 mg/kg) ip injections and were repeated daily for 2, 5 or 20 subsequent days. Rats were killed 2, 5 and 20 days after ip injections, and blood and urine samples were collected to determine plasma creatinine, urine volume and osmolality. The kidneys were removed to determine the levels of thiobarbituric acid-reactive substances (TBARS) and for histological studies. Cisplatin increased lipid peroxidation, urine volume and plasma creatinine levels and decreased urine osmolality. Treatment with quercetin attenuated these alterations. These results demonstrate the role of oxidative stress and suggest a protective effect of quercetin on cisplatin-induced nephrotoxicity in adult Wistar rats.

Protective effect of quercetin on the evolution of cisplatin-induced acute tubular necrosis.

BACKGROUND: The mechanism of cisplatin-induced nephrotoxicity is unknown, but has been associated with renal lipid peroxidation. The bioflavonoid quercetin may be a potential alternative to reduce cisplatin-induced nephrotoxicity. The aim of this study was to evaluate the effect of quercetin on the evolution of cisplatin-induced acute tubular necrosis. METHODS: One hundred and three male Wistar rats were injected with cisplatin (5 mg/kg, i.p.), 43 of them received quercetin (50 mg/kg, by gavage) before cisplatin injection. Blood and urine were collected 5 and 20 days after the injection for the determination of plasma creatinine, urine volume and osmolality. The kidneys were removed for the determination of renal malondialdehyde (MDA) and for histological and immunohistochemical studies. The renal expression of fibronectin, alpha-smooth muscle actin, vimentin, Jun N-terminal kinase, nuclear factor-kappaB, and macrophages during the evolution of the acute tubular necrosis induced by cisplatin and the histological changes observed in the kidneys were analyzed. RESULTS: Cisplatin-treated rats presented a transitory increase in plasma creatinine levels, tubular cell necrosis and increased immunostaining for vimentin, alpha-SM-actin, fibronectin, ED1, NF-kappaB, and p-JNK in the renal cortex and outer medulla. These alterations were less intense in animals treated with quercetin. CONCLUSION: Quercetin treatment attenuated the functional, histological and immunohistochemical alterations induced by cisplatin.

Interstitial alterations in renal cortex in acute tubular necrosis (ATN) post-renal transplantation and in patients with ATN not related to renal transplant.

BACKGROUND: Abnormalities of renal function with long-term implications can persist after acute tubular necrosis (ATN), probably because of permanent loss of nephrons. Residual areas of fibrosis are also observed in the renal cortex post-ATN. In this study, we investigate the interstitial alterations post-ATN using histological and immunohistochemical methods. METHODS: We studied 11 patients with ATN of different etiologies and 19 patients with ATN post-renal transplantation. Eleven patients with ATN post-renal transplantation and one with ATN not related to renal transplantation were submitted to more than one biopsy because of delayed renal function recovery. The immunohistochemical studies were performed using alpha-smooth muscle-actin (alpha-SM-actin), endothelin, nuclear factor-kappaB (NF-kappaB), Jun-N-terminal kinase (p-JNK) and fibronectin antibodies. We also analyzed the urinary content of transforming growth factor-beta (TGF-beta) during the acute phase of ATN. RESULTS: The immunohistochemical studies showed increased alpha-SM-actin, fibronectin, endothelin, p-JNK and NF-kappaB staining in the tubulointerstitium area from the renal cortex of all patients when compared with controls (p < 0.001), and these increase persisted in the patients submitted to sequential biopsies. One of the patients with ATN without renal transplant and six patients with ATN post-renal transplant developed chronic renal failure. There was a significant increase of TGF-beta excretion in the urine of patients with acute renal failure (p < 0.01) compared with control. CONCLUSIONS: Our data show that the enhancement of renal TGF-beta production and the persistent increase of myofibroblasts, fibronectin, endothelin, p-JNK and NF-kappaB in renal cortex tubulointerstitium post-ATN may explain the impaired recovery of renal function observed in patients post-ATN frequently observed in patients with ATN post-renal transplant.

Inhibition of nuclear factor-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin.

BACKGROUND: Animals treated with gentamicin can show residual areas of interstitial fibrosis in the renal cortex. This study investigated the expression of nuclear factor-kappaB (NF-kappaB), mitogen-activated protein (MAP) kinases and macrophages in the renal cortex and structural and functional renal changes of rats treated with gentamicin or gentamicin + pyrrolidine dithiocarbamate (PDTC), an NF-kappaB inhibitor. METHODS: 38 female Wistar rats were injected with gentamicin, 40 mg/kg, twice a day for 9 days, 38 with gentamicin + PDTC, and 28 with 0.15 M NaCl solution. The animals were killed 5 and 30 days after these injections and the kidneys were removed for histological and immunohistochemical studies. The results of the immunohistochemical studies were scored according to the extent of staining. The fractional interstitial area was determined by morphometry. RESULTS: Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. Increased ED-1, MAP kinases and NF-kappaB staining were also observed in the renal cortex from all gentamicin-treated rats compared to control (p < 0.05). The animals killed on day 30 also presented fibrosis in the renal cortex despite the recovery of renal function. Treatment with PDTC reduced the functional and structural changes induced by gentamicin. CONCLUSIONS: These data show that inhibition of NF-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin.