Henoch-Schönlein Nephritis Manifesting with Purpura 15 years after Diagnosis of IgA Nephropathy.

Henoch-Schönlein nephritis or immunoglobulin A (IgA) vasculitis is characterized by purpura, arthralgia, abdominal pain, and glomerulonephritis with glomerular IgA deposition. Notably, the presence of purpura is essential to diagnose this disease. We report the case of a patient in whom proteinuria and haematuria were detected during screening tests and he was diagnosed with IgA nephropathy at 20 years of age. Corticosteroids were administered for 7 years and were subsequently tapered. At 35 years of age, he noticed purpura on his lower extremities and was diagnosed with anaphylactoid purpura. Following the appearance of purpura, urinalysis revealed an increase in urinary protein levels from 0.7 g/g creatinine (Cr) to 1.4 g/gCr, and his serum Cr levels increased from 1.1 mg/dL to 1.35 mg/dL. Two months later purpura subsided, and his urinary protein level and serum Cr level were restored to the former levels. Although the cause remains unknown, an interval may occasionally be observed between the appearance of purpura and urinary abnormalities. However, to our knowledge to date, a 15-year interval is the longest interval, in such cases, reported in the literature.

Minimal Change Nephrotic Syndrome Relapse after 52 Years of Remission: A Case Report.

Minimal change nephrotic syndrome (MCNS) is the most common cause of nephrotic syndrome in children and can also present in adults. Corticosteroids generally induce remission of MCNS, and relapses are common after reduction or discontinuation of corticosteroids. We experienced a rare case of steroid-sensitive MCNS where the patient relapsed after 52 years of remission. The patient was a 61-year-old Japanese male who visited our clinic for an edema of the lower extremities which had already persisted for a few days. Laboratory testing showed massive urinary protein and low serum total protein and albumin levels. Therefore, he was diagnosed with nephrotic syndrome. He had a history of nephrotic syndrome that initially developed when he was 5 years old. Although corticosteroids reduced the urinary protein level, frequent relapses occurred when their doses were reduced, or when they were discontinued. He had previously experienced a relapse when he was 9 years old. For his current condition, treatment with corticosteroids and diuretics for 1 week reduced his edema and proteinuria. We suspected that this is a case of MCNS and that the present event is a relapse. Thus, we concluded that this is a very rare case of steroid-sensitive nephrotic syndrome that relapsed after 52 years of remission.

Roxithromycin inhibits transforming growth factor-beta production by cultured human mesangial cells.

BACKGROUND: Transforming growth factor-beta (TGF-beta) plays an important role in progression of renal injury. However, few materials which inhibit TGF-beta have been known. Roxithromycin (ROX), macrolide antibiotics, is known to have anti-inflammatory, immunomodulatory and tissue reparative effects besides its bacteriostatic activity, although the exact mechanism of its anti-inflammatory and immunomodulatory effects was not defined. We examined the effect of ROX on production of TGF-beta and type IV collagen by cultured human mesangial cells (HMC). METHODS: Human mesangial cells were incubated with several concentrations of ROX and TGF-beta and type IV collagen levels in the culture supernatants were measured by enzyme-linked immunoassay. Amount of TGF-beta mRNA was also quantified by using a colourimetric mRNA quantification kit and semiquantitative reverse transcriptase polymerase chain reaction. We also examined the effect of ROX on tyrosine kinase, MAP kinase and NF-kappaB stimulated by thrombin. RESULTS: Roxithromycin (0.1-10.0 microg/mL) inhibited TGF-beta production by HMC in a dose- and time-dependent manner without inducing cell injury. ROX (10.0 microg/mL) also inhibited mRNA expression of TGF-beta in HMC. Thrombin (5 U/mL) stimulated TGF-beta production by HMC and ROX significantly inhibited the stimulating effect of thrombin on TGF-beta production. ROX also inhibited the increment of type IV collagen production stimulated by thrombin. ROX (10.0 microg/mL) suppressed the thrombin-induced NF-kappaB activation, although ROX did not inhibit the activation of tyrosine kinase and MAP kinase by thrombin. CONCLUSION: Roxithromycin has an inhibitory effect on TGF-beta production by HMC possibly via inhibition of NF-kappaB. ROX may be a potential agent for the treatment of glomerulosclerosis.

Thrombin stimulates production of fibronectin by human proximal tubular epithelial cells via a transforming growth factor-beta-dependent mechanism.

BACKGROUND: Tubulointerstitial fibrosis contributes to the progression of many forms of glomerular disease and to end-stage renal failure. Inflammatory mediators generated during glomerular injury may induce tubulointerstitial lesions by stimulating tubular cells. Thrombin has multiple biological functions in addition to its role in haemostasis and has been detected in the urine of patients with glomerular diseases. The present study investigated whether thrombin can modulate the production of fibronectin (FN) in cultured human proximal tubular epithelial cells (PTEC). METHODS: Cultured PTEC were incubated with or without thrombin to examine the effect of thrombin on FN production in PTEC. FN and transforming growth factor-beta (TGF-beta) levels were measured in culture supernatants by enzyme-linked immunosorbent assay (ELISA). Expression of FN mRNA was analysed by reverse transcriptase-polymerase chain reaction. Effects of thrombin on matrix metabolism were examined by enzyme immunoassay for the detection of secreted matrix metalloproteinase (MMP) and its inhibitors (TIMPs) as well as by zymography. RESULTS: Thrombin stimulated FN secretion in PTEC. Thrombin also stimulated TGF-beta secretion in PTEC in a dose-dependent manner. Expression of FN mRNA by PTEC was augmented by thrombin. The stimulatory effect of thrombin on FN secretion was inhibited by neutralizing antibodies against TGF-beta but not by an irrelevant antibody. Thrombin-induced FN secretin was also inhibited by thrombin inhibitors, such as antithrombin III, hirudin and argatroban. Although thrombin stimulated TIMP-1 and -2 secretion by PTEC, the stimulatory effect of thrombin on MMP-2 was not statistically significant. Thrombin did not affect the expression of MMP-2 in zymography studies. CONCLUSIONS: We found that thrombin stimulates FN production in PTEC without causing matrix degradation, an effect that may contribute to the formation of tubulointerstitial fibrosis associated with glomerular disease. The stimulatory effect of thrombin on FN production in PTEC is, at least in part, mediated by TGF-beta.

Tissue factor pathway inhibitor production by human proximal tubular epithelial cells in culture.

Fibrin deposition in the peritubular capillaries and along the tubular basement membrane is commonly observed in several renal diseases and suggests the involvement of blood coagulation in tubulointerstitial damage. It has been demonstrated that tissue factor (TF) is present in tubular epithelial cells of animal models of nephritis. Tissue factor pathway inhibitor (TFPI) regulates the extrinsic pathway of blood coagulation through its ability to inhibit TF activity and it is now thought to be produced mainly by the vascular endothelial cells. We examined whether human proximal tubular epithelial cells (PTEC) could produce TFPI and attempted to clarify the regulatory factors affecting TFPI production. Cultured human PTEC were used. The procoagulant activity (PCA) in PTEC lysate was quantified by measurement of the one-stage recalcification time. TFPI in the cell supernatants was measured by ELISA. The mRNA of TF and TFPI in PTEC was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). PCA which is compatible with TF activity was present in the PTEC lysate. TF mRNA and TFPI mRNA were detected in PTEC. The amount of TFPI increased over time in the cell supernatants. Immnoblot analysis revealed 40 kD protein of TFPI, and TFPI antigen was demonstrated in PTEC by immunofluorescence. The concentration of TFPI was significantly increased following incubation with thrombin and heparin in a dose- and time-dependent manner, although the amount of TFPI mRNA was not changed. Our study showed that TFPI is produced in cultured PTEC and added one more cell type that produced TFPI other than endothelial cells. Thrombin and heparin stimulated TFPI secretion from PTEC. TFPI of PTEC may act against generation of thrombin and tubular fibrin formation induced by tissue factor activation. The augmentation of TFPI secretion by heparin may play an important role in the modulation of anticoagulant properties of PTEC.

Eotaxin level in induced sputum is increased in patients with bronchial asthma and in smokers.

BACKGROUND: Airway eosinophilia is one of the hallmarks of asthma. Eotaxin may play an important role in eosinophil recruitment. OBJECTIVES: To examine the relationship between eotaxin levels in the sputum and eosinophilic inflammation. METHODS: The sputum was obtained from 11 non-smokers, 14 smokers and 13 asthmatic patients using a sputum induction method. Eotaxin and interleukin (IL)-5 levels in the sputum were determined by ELISA and immunocytochemical analysis. RESULTS: Asthmatic patients had eosinophilia and smokers showed neutrophilia in their sputum. The eotaxin level in the sputum was significantly higher in smokers (median 412.5, range 91.1-872.2 pg/ml) and asthmatic patients (351.0, 185.0-928.0 pg/ml) compared with non-smokers (123.2, 0-369.0 pg/ml; both p < 0.05). IL-5 was detected in the sputum of 1 non-smoker, none of the smokers and 4 asthmatic patients. The percentage of eotaxin-positive cells was higher in smokers and asthmatic patients than in non-smokers, but the percentage of IL-5-positive cells was significantly higher only in asthmatic patients (p < 0.05). CONCLUSIONS: These findings suggest that the elevated eotaxin level in the sputum does not always accompany the increase in eosinophils, and cooperation with another cytokine such as IL-5 may be required for the recruitment of eosinophils.