Tubulointerstitial nephritis and uveitis syndrome in children: report of three cases / Nefrite tubulointersticial e uveíte em idade pediátrica: descrição de três doentes

ABSTRACT Tubulointerstitial nephritis and uveitis syndrome is a rare and probably underdiagnosed condition. Renal and ocular manifestations may not occur simultaneously, making the diagnosis more difficult. Nephritis may be asymptomatic; therefore, renal function evaluation is essential for diagnosis. Urinary β2-microglobulin levels may be particularly useful. Uveitis, mostly anterior, nongranulomatous and bilateral, occurs usually after the onset of nephritis. Treatment includes corticosteroids and, eventually, other immunosuppressant agents. Renal disease is usually benign and resolves spontaneously or after treatment with systemic corticosteroids. Uveitis, however, may be chronic or recurrent. The authors described the cases of three pediatric patients diagnosed with tubulointerstitial nephritis and uveitis syndrome. The goal of this paper was to warn the medical community over the need to screen patients with uveitis for renal disease.

RESUMO A síndrome nefrite tubulointersticial e uveíte é uma doença rara, provavelmente subdiagnosticada. As manifestações renais e oculares podem não ocorrer simultaneamente, tornando o diagnóstico mais difícil. A nefrite é geralmente assintomática, tornando fundamental a avaliação da função renal em doentes com uveíte. O doseamento da excreção urinária de β2-microglobulina é particularmente útil para o diagnóstico. A uveíte, tipicamente anterior, não granulomatosa e bilateral, manifesta-se após a nefrite na maioria dos casos. O tratamento inclui corticoides e, por vezes, outros imunossupressores. A doença renal tem evolução benigna, resolvendo-se espontaneamente ou com terapêutica com corticoides sistêmicos na maioria dos casos, no entanto, a uveíte pode ser crônica ou recorrente. Os autores descrevem três casos de síndrome nefrite tubulointersticial e uveíte, diagnosticados em idade pediátrica, e pretendem alertar para a necessidade de pesquisar sempre alterações renais nos doentes com uveíte.

Baicalein alleviates tubular-interstitial nephritis in vivo and in vitro by down-regulating NF-κB and MAPK pathways

Tubular-interstitial nephritis (TIN) is characterized by tubular cell damage and inflammatory lesions of kidneys. Baicalein (BAI) is a flavonoid compound found in the roots of Scutellaria baicalensis Georgi. The present study was undertaken to explore the anti-inflammatory and anti-oxidative effects of BAI on TIN patients and a lipopolysaccharide (LPS)-induced TIN cell model. The expression levels of interleukin-6 (IL-6), IL-10, and tumor necrosis factor α in serum samples of TIN patients and culture supernatants of renal proximal tubular epithelial cells (RPTECs) were evaluated using enzyme-linked immunosorbent assay. Creatinine clearance was calculated using the Cockcroft-Gault equation. Activities of malondialdehyde, superoxide dismutase, and glutathione peroxidase were also determined. Viability and apoptosis of RPTECs were measured using MTT assay and Guava Nexin assay, respectively. qRT-PCR was performed to determine the expressions of Bax, Bcl-2, nuclear factor kappa B (IκBα), and p65. Protein levels of Bax, Bcl-2, IκBα, p65, c-Jun N-terminal kinase, extracellular regulated protein kinases, and p38 were analyzed using western blotting. We found that BAI reduced inflammation and oxidative stress in vivo and in vitro. Moreover, BAI alleviated the LPS-induced RPTECs viability inhibition and apoptosis enhancement, as well as nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) activation. Phorbol ester, an activator of NF-κB, attenuated the effects of BAI on LPS-induced inflammatory cytokine expressions in RPTECs. In conclusion, BAI had anti-inflammatory and anti-oxidative effects on TIN patients and LPS-induced RPTECs by down-regulating NF-κB and MAPK pathways.

Megalocytic Interstitial Nephritis Following Acute Pyelonephritis with Escherichia coli Bacteremia: A Case Report

Megalocytic interstitial nephritis is a rare form of kidney disease caused by chronic inflammation. We report a case of megalocytic interstitial nephritis occurring in a 45-yrold woman who presented with oliguric acute kidney injury and acute pyelonephritis accompanied by Escherichia coli bacteremia. Her renal function was not recovered despite adequate duration of susceptible antibiotic treatment, accompanied by negative conversion of bacteremia and bacteriuria. Kidney biopsy revealed an infiltration of numerous histiocytes without Michaelis-Gutmann bodies. The patient's renal function was markedly improved after short-term treatment with high-dose steroid.

Alkali Therapy Attenuates the Progression of Kidney Injury via Na/H Exchanger Inhibition in 5/6 Nephrectomized Rats

Metabolic acidosis is a cause of renal disease progression, and alkali therapy ameliorates its progression. However, there are few reports on the role of renal acid-base transporters during alkali therapy. We evaluated the effect of sodium bicarbonate therapy and the role of acid-base transporters on renal disease progression in rats with a remnant kidney. Sprague-Dawley rats consumed dietary sodium bicarbonate (NaHCO3) or sodium chloride (NaCl) with 20% casein after a 5/6 nephrectomy. After being provided with a casein diet, the NaHCO3-treated group had higher levels of serum bicarbonate than the control group. At week 4, the glomerular filtration rate in the NaHCO3 group was higher than that in the NaCl group, and the difference became prominent at week 10. The glomerulosclerosis and tubulointerstitial damage indices in the NaHCO3 group were less severe compared with controls at week 4 and 10. The expression of the Na/H exchanger (NHE) was decreased, and apical reactivity was decreased in the NaHCO3 group, compared with the NaCl group. Endothelin-1 levels in the kidney were also decreased in the NaHCO3 group. Dietary sodium bicarbonate has the effects of ameliorating renal disease progression, which may be related to the altered expression of NHE in the remaining kidney.

Reversible acute renal failure due to Chinese herbs

Recently, herb induced nephropathy has been described as a subgroup of renal disorders. Patients taking Chinese herbs for eczema and weight reduction have been reported to develop chronic interstitial nephritis, rapidly progressive interstitial fibrosis and urothelial malignancies. An agent, known as aristolochic acid [AA], isolated from such herbs has been identified as an independent and direct nephrotoxin. The pathology by which AA incurs renal damage is yet to be determined. With regards to malignancies triggered by such herbs, these patients have been found to over express a mutated p53 gene. Here, we discuss the management of a young female patient who developed biopsy proven acute interstitial nephritis with early fibrosis after ingesting a herbal remedy for a short period of time. Other causes of interstitial nephritis in this patient such as viral infections and autoimmune disorders were investigated and ruled out. Initially, she presented with acute renal failure requiring hemodialysis for ten days. Fortunately, she did not develop any permanent renal dysfunction as the etiology was identified early and the herbs were discontinued immediately. Her renal impairment reversed to normal within a one-month period after a trial of corticosteroids was administered. We believe this is the first of such cases isolated in Saudi Arabia

Citrate attenuates tubulointerstitial fibrosis in 5/6 nephrectomized rats by decreasing transforming growth factor-beta1.

OBJECTIVE: Tubulointerstitial fibrosis plays an essential role in progression to end stage renal disease (ESRD) in various chronic renal failure (CRF) models including the 5/6 nephrectomy (5/6). The present study examines the renoprotective effect of citrate in the renal ablative model that is quite similar to CRF in human. MATERIAL AND METHOD: Male Wistar rats underwent 5/6 and were fed with tap water (5/6tap) or tap water containing 67 mEq/L citrate solution (5/6cit). Sham-operated rats (S) were divided into Stap and Scit groups. Renal function, renal histopathology, renal alpha-Smooth muscle actin (SMA), and renal transforming growth factor (TGF)-beta1 were determined immediately and at the 8th week after operation. RESULTS: Following the surgery, the values of glomerular filtration rate (GFR) in the 5/6tap and the 5/6cit groups were 2.39 +/- 0.25 and 2.35 +/- 0.25 (mL/kg/min), respectively, both were significantly lower than sham groups (p < 0.05). At the eighth week, the 5/6tap group had progressively decreased GFR and had higher fibrosis score, increased alpha-SMA positive cells, and renal tissue TGF- beta1 when compared with the sham groups. The 5/ 6cit group, when compared with the 5/6tap group, had higher GFR (2.51 +/- 0.22 vs 1.17 +/- 0.33 mL/kg/min; p < 0.05), lower fibrosis score (1.83 +/- 0.88 vs 3.0 +/- 0.4, p < 0.001), lower alpha-SMA activity (159 +/- 2.9 vs 187 +/- 12.3 cells per 1000 interstitial cells, p < 0.05), and lower renal TGF-beta1 levels (1771.3 +/- 239.5 vs 4716.9 +/- 871.2 pg/mg protein, p < 0.005). CONCLUSION: As such, in 5/6 nephrectomized rats, citrate therapy for eight weeks could decrease tubulointerstitial fibrosis mainly by reducing the heightened renal TGF-beta1 levels and additionally by attenuating the increased myofibroblast activity.

Granulomatous interstitial nephritis in renal transplant recipient.

Tuberculosis of a transplanted kidney is a rare and serious complication. Search for renal tuberculosis as the cause of deterioration of graft function is mandatory in a renal transplant recipient with tuberculosis of other organs e.g. pulmonary tuberculosis in this patient. Renal histopathology is required for the diagnosis. Treatment with anti-tuberculosis drugs can improve renal function. Drug interactions should be considered when rifampicin is administered with cyclosporin A.

Infecçäo aguda do trato urogenital / Acute infection of the genitourinary system

Os autores fazem uma abordagem prática sobre o diagnóstico e o tratamento de pacientes com infeccao aguda do trato urogenital. Säo apresentadas as situaçöes mais comuns relacionadas à infecçäo do trato urinário baixo e do rim, assim como algumas das infecçöes sexualmente transmissíveis. Procurou-se, em cada situaçäo, comentar sobre os agentes etiológicos mais freqüentes, bem como orientar a solicitaçäo de exames subsidiários pertinentes para a confirmaçäo do diagnóstico, para a identificaçäo de complicaçäo ou de fatores predisponentes. Recomendou-se, ainda, a terapia específica mais usada para cada caso, näo só para combater os agentes infecciosos mais também os fatores predisponentes e as complicaçöes

Sucesso terapêutico com uso de esteróide em um caso de nefrite intersticial aguda secundária à rifampicina / Therapeutic success with use of steroid in a case of acute interstitial nephritis secondary to rifampin

O uso de corticosteróides e/ou outras drogas imunossupressoras no tratamento de nefrite intersticial aguda (NIA) permanece controverso. Os autores relatam um caso de NIA, secundária ao uso de rifampicina, tratado com prednisona, no qual se obteve excelente resposta: paciente feminina com diagnóstico de tuberculose pulmonar, que se apresentava com funçäo renal normal, foi submetida a terapêutica tríplice (rifampicina e pirazinamida). No quadragésimo dia de tratamento, mostrou creatinina de 2,4mg/dl e BUN de 27mg/dl; após três dias, foi submetida a exames que mostraram: creatinina plasmática, 5,5mg/dl; nitrogênio uréico plasmático, 74mg/dl; sódio urinário, 78mEq/1; osmolalidade urinária, 416mOsm/Kg de H2O e fraçäo de excreçäo de sódio de 4,3%; exame do sedimento urinário com leucocitúria, hematúria e eosinofilúria; proteinúria de 24 horas de 900mg; ultra-som renal normal. A biopsia renal revelou tratar-se de NIA, sendo suspensa a rifampicina e, como a funçäo renal continuava a piorar, iniciou-se prednisona. Houve estabilizaçäo dos níveis de escórias nitrogenadas e queda a partir do quarto dia de tratamento, recebendo alta hospitalar com funçäo renal normal