Diclofenac-associated acute renal failure. Report of 2 cases

2 cases of acute renal failure associated with diclofenac therapy are reported. In the 1st case no other risk factors but diclofenac administration were identified. Renal biopsy showed patchy interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. In the 2nd case preexisting nephropathy and heart failure were underlying illnesses. In both cases renal function returned to the basal values after stopping the drug.     

Multiple lesions of cutaneous focal mucinosis in a teenager

A 19-year-old Hispanic woman presented to our clinic with a chief complaint of multiple pink papules on her face (Figure 1). The lesions were asymptomatic, had appeared several years before her consultation, and had remained stable in size. Similar lesions on her trunk and extremities had spontaneously resolved before presentation. She had no significant medical history and was not on any medications. Cutaneous examination was remarkable for a few scattered, well-demarcated, slightly raised pink papules and plaques with no scale, ranging from 0.5 to 1 cm in diameter. The lesions were distributed on the right cheek, right temple, left lower eyelid, and neck area. The rest of the cutaneous examination was unremarkable. A punch biopsy was performed from a lesion near the left premandibular area. Hematoxylin and eosin staining of the biopsy specimen revealed superficial perivascular dermatitis with a slight increase in the number of fibroblasts (Figure 2). Colloidal iron staining was diffusely positive with replacement of collagen with mucinous material in the dermal layer (Figure 3). Laboratory values for a complete blood cell count, metabolic panel, serum protein electrophoresis, urine protein electrophoresis, thyroid-stimulating hormone, and antinuclear antibody were within normal limits. The patient was diagnosed with cutaneous focal mucinosis. Because of cosmetic concerns, the patient declined surgical excision and intralesional corticosteroid injections. A 4-month trial of topical tacrolimus 0.1% ointment was ineffective.     

Desquamative interstitial pneumonia: relationship to interstitial fibrosis

Patchefsky, A. S., Israel, H. L., Hoch, W. S., and Gordon, Gloria (1973).Thorax, 28, 680-693. Desquamative interstitial pneumonia: relationship to interstitial fibrosis. The clinical course and radiographic and pathological findings in 14 patients having the histological pattern of desquamative interstitial pneumonia (DIP) have been studied. Four deaths occurred from cardiorespiratory failure and two from other diseases, and one patient has severe pulmonary insufficiency. Seven patients had altered immunological reactivity or arthritis.     

Sodium-valproate-induced interstitial nephritis

A 5-year-old Chinese girl had had absence seizures and received sodium valproate (VPA) treatment which provided good control. Six months later, she developed interstitial nephritis with proteinuria and microhematuria. Renal biopsy revealed interstitial nephritis with granular deposition of immunoglobulin G (IgG) and C3 in the renal tubular basement membrane (TBM). Ultrastructurally, dilated smooth endoreticular cisternae with mitochondrial degeneration in the tubular cells and scattered electron-dense deposits within the TBM were also noted. Serum circulating immune complexes were detectable, ACH50 and properdin factor B increased. Mononuclear cells (MNC) from the patient after in vitro incubation with VPA (100 micrograms/ml) induced interleukin-2 (IL-2) production and lymphoproliferative response. However, there was no response in controls. The serum VPA level ranged from 84 to 92 micrograms/ml. After VPA was stopped, the microhematuria and proteinuria disappeared. These observations indicate that VPA-induced interstitial nephritis represents a sequence of interrelationships among multiple immunologic factors.     

Mesalazine-associated interstitial nephritis

BACKGROUND.: When used for oral treatment of inflammatory bowel disease,Asacol (a coated form of mesalazine = 5-aminosalicylic acid)can cause interstitial nephritis. The spectrum of severity,frequency of occurrence and the best renal function test todetect this complication are not known. The value of immunosuppressionin addition to drug withdrawal is similarly undetermined. METHODS.: Four cases of interstitial nephritis which occurred in associationwith oral Asacol treatment are presented and a further 12 caseswho received similar treatment are reviewed. Clinical trialspublished previously were scrutinized to assess the frequencyof impaired renal function. RESULTS.: The available evidence suggests that renal impairment of anyseverity may occur in up to 1 in 100 patients, but that clinicallysignificant interstitial nephritis occurs in less than 1 in500 patients. This is most reliably detected by an elevatedserum creatinine concentration. If the diagnosis of nephrotoxicityis delayed until 18 months after commencement of medication,restoration of renal function, which is seen on withdrawal ofmedication alone up to 10 months, does not occur and there isno evidence to date to indicate that addition of immunosuppressionconfers any significant advantage at this later stage. CONCLUSIONS.: It is suggested that serum creatinine concentration should bemeasured each month for the first 3 months of treatment, 3-monthlyfor the remainder of the first year and annually thereafter.The use of concurrent immunosuppressive therapy may necessitateextension to the period of intensive monitoring. Any elevationof serum creatinine which cannot be related to a relapse ofinflammatory bowel disease should prompt immediate withdrawalof Asacol and related medications and substitution of alternativetherapy. Neither the lack of urinary abnormalities on routinetesting nor the absence of clinical or laboratory features ofdrug allergy can be relied upon to rule out interstitial nephritisduring oral therapy with these drugs.     

肥大细胞与间质性肾炎间质纤维化的关系

目的探讨急性间质性肾炎(AIN)、慢性间质性肾炎(CIN)肾间质中肥大细胞(MCs)浸润与间质纤维化之间的关系。方法随机选取患者肾穿刺组织作为研究样本。其中AIN组11例，CIN组16例，另选取微小病变病(MM)11例作为对照组，采用组织化学、免疫组织化学、免疫荧光双重染色方法观察MCs、蛋白酶活化受体-2(PAR-2)、转化生长因子-β1(TGF—β1)及Ⅰ型胶原(ColⅠ)在肾组织中的表达变化。结果(1)与MM对照组相比，AIN、CIN组肾间质。MCs数量明显增加。(2)MCs数量与肾小管上皮细胞PAR-2和TGF-β1表达面积及肾间质ColⅠ表达面积呈显著正相关；肾小管上皮细胞PAR-2与TGF-β1表达面积间也呈显著正相关。(3)MCs数量分别与肾间质PAR-2和TGF-β1阳性细胞数量呈显著正相关，MCs与肾间质PAR-2或TGF-β1染色阳性细胞存在部分重叠。结论。MCs可能参与AIN、CIN细胞外基质蓄积。其机制可能是通过活化．PAR-2．增加TGF-β1表达，促进ColⅠ合成。