Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis.

OBJECTIVES: The treatment of pure membranous (class V) lupus nephropathy remains unsatisfactory. We studied the efficacy and safety of tacrolimus in the treatment of membranous nephritis secondary to SLE. METHODS: We recruited 18 consecutive SLE patients (tacrolimus group) with recently confirmed biopsy-proven class V lupus nephritis. They were treated with a tailing dose of oral prednisolone and tacrolimus 0.1-0.2 mg/kg/day for 6 months, followed by maintenance prednisolone and AZA. The rate of resolution of proteinuria and SLEDAI were compared with 19 historical controls treated with oral cyclophosphamide or AZA (control group). All patients were followed for 12 months. RESULTS: Baseline clinical characteristics were comparable between the groups. For the tacrolimus group, the complete and partial remission rates were 27.8 and 50.0%, respectively at 12 weeks; for the control group, they were 15.8 and 47.4%, respectively (overall chi-square test, P = 0.5). However, tacrolimus group had faster resolution of proteinuria than the control group by the general linear model with repeated measures (P = 0.032). At 12 weeks, proteinuria was reduced by 76.2 +/- 17.0% for the tacrolimus group and 47.1 +/- 51.1% for the control group (P = 0.028). Serial change in renal function and SLEDAI score did not differ between the groups. During the study period, four patients of the tacrolimus group, and 11 of the control group, developed lupus flare (P = 0.027). There was no serious adverse effect in the tacrolimus group. CONCLUSIONS: A 6-month course of tacrolimus is a safe and effective treatment of pure class V (membranous) lupus nephritis. As compared with conventional cytotoxic treatment, tacrolimus possibly results in a faster resolution of proteinuria, and a lower risk of lupus flare within 1 yr. The long-term effect and optimal regimen of tacrolimus require further study.

Ventricular bigeminy during phenylephrine infusion used to maintain normotension during caesarean section under spinal anaesthesia.

A 31-year-old primiparous, healthy woman presented for emergency caesarean section. Following the siting of a spinal anaesthetic, seconds after starting a phenylephrine infusion, she developed ventricular bigeminy. She reverted to sinus rhythm spontaneously when the phenylephrine infusion was stopped at delivery. The possible proarrhythmic and antiarrhythmic effects of phenylephrine are discussed. We suggest that this was most probably a stretch-induced ventricular arrhythmia due to increased ventricular afterload.

Chromosomal telomere shortening of kidney cells in IgA nephropathy by the measurement of DNA in urinary sediment.

BACKGROUND: The histology and function of the kidney deteriorates with age and progressive renal failure, but the mechanisms involved in renal ageing are not known. In vitro studies suggest that telomere shortening is important in replicative senescence, and is accelerated by stress factors that increase replication. We investigated whether IgA nephropathy, a prototype chronic kidney disease, is associated with localized intrarenal cellular ageing. METHODS: We studied the mean length of terminal restriction fragments (TRF), a measure of average telomere size, in the DNA of peripheral blood mononuclear cells and urinary sediment of 15 patients with IgA nephropathy. RESULTS: The mean TRF lengths in peripheral blood is 7043.8 +/- 1 182.8 base pairs, and in urinary sediment is 6 749.7 +/- 636.5 base pairs. The mean TRF lengths of urinary DNA significantly correlate with the serum creatinine (r = -0.525, p = 0.044) and estimated glomerular filtration rate (GFR) (r = 0.651, p = 0.009). The mean TRF lengths of urinary DNA had an insignificant inverse correlation with patient age (r = -0.364, p = 0.2), and do not correlate with the degree of glomerulosclerosis (r = 0.004, p = 0.9) or tubulointerstitial scarring in renal biopsy (r =-0.032, p = 0.9). After 30 months of follow-up, the rate of decline of estimated GFR has an inverse correlation with the mean TRF lengths of urinary DNA (r = -0.699, p = 0.004). The TRF lengths of peripheral blood DNA do not correlate with any clinical or histological parameter or the rate of renal function decline. CONCLUSIONS: Although this is a pilot study, our observation indicates that the TRF lengths of genomic DNA extracted from urinary sediment is related to the degree of renal impairment. However, a long telomere length of genomic DNA in urinary sediment is associated with a more rapid decline of renal function. Our findings might be relevant to the pathogenesis of progressive renal failure.

The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria.

PURPOSE: To determine the natural history of immunoglobulin (Ig) A nephropathy among patients who presented with hematuria and minimal proteinuria, and factors associated with the development of adverse clinical events, such as proteinuria. SUBJECTS AND METHODS: In Hong Kong, all patients who present with isolated hematuria are referred for renal biopsy after urologic diseases are ruled out. We reviewed the clinical course of 72 consecutive patients with histologically confirmed IgA nephropathy who presented with hematuria and minimal proteinuria (0.4 g/day or less). All patients were normotensive and had normal renal function at presentation. Adverse events were defined as proteinuria greater than 1 g per day, hypertension, or impaired renal function (serum creatinine level 120 micromol/L or estimated creatinine clearance < 70 mL per minute). RESULTS: The mean (+/- SD) age at presentation was 27 +/- 8 years; 56 (78%) were female. Nine patients (13%) had grade 2 histologic lesions. During a median follow-up of 7 years, 32 patients (44%) developed adverse events: 24 (33%) developed proteinuria of 1 g per day or more, 19 (26%) became hypertensive, and 5 (7%) developed impaired renal function. Another 30 patients (42%) had persistently abnormal urinalysis examinations. Only 10 patients (14%) had complete resolution of hematuria. The median time for progression from proteinuria (> l g/day) to renal impairment was 84 months (range 56 to 132). In a multivariate analysis, age at presentation (relative risk [RR] per 10 years of age = 2.0; 95% confidence interval [CI], 1.2 to 3.4) and histologic grade (grade 2 versus grade 1, RR = 4.5; 95% CI, 1.7 to 12) were independent predictors of developing an adverse event. CONCLUSIONS: IgA nephropathy that presents with hematuria and minimal proteinuria is usually a progressive disease. Life-long follow-up with regular monitoring of blood pressure and proteinuria is recommended.

Primary glomerulonephritis with detectable glomerular hepatitis B virus antigens.

The glomerular pathology and hepatitis B virus (HBV) antigens in renal biopsies were investigated in 100 consecutive patients with both primary glomerulonephritis and positive serology for hepatitis B surface antigen (HBsAg). Glomerular HBV antigens including HBsAg, hepatitis B core antigen (HBcAg), and hepatitis B e antigen (HBeAg) were examined in frozen tissue using both polyclonal and monoclonal antibodies. HBV serology and glomerular antigens were correlated. Using monoclonal antibodies, at least one of the three HBV antigens was detectable in glomeruli in 39% of the cases. These findings correspond mainly to detectable glomerular HBsAg and HBeAg in 22.3 and 28.4% of cases, respectively. A good correlation was found between glomerular and serum HBeAg but not observed for HBsAg. Serum HBcAg was not examined and not correlated with glomerular staining. When the diagnosis of HBV-related glomerulonephritis was based strictly on detectable glomerular antigens, three distinctive morphologies were identified: membranous nephropathy, mesangiocapillary glomerulonephritis, and mesangial proliferative glomerulonephritis with immunoglobulin A (IgA) deposits (IgA nephropathy). Each of these lesions may be seen in pure form or occasionally in overlapping form leading to double glomerulopathies. Glomerular HBeAg and HBsAg were associated with subepithelial and mesangial immune complexes, respectively. Rare overlap between membranous nephropathy and IgA nephropathy further emphasized the distinctive pathology of HBV-related glomerulonephritis and the independent etiological role of HBeAg and HBsAg. In other glomerulonephritis, which rarely demonstrated glomerular HBV antigens, the pathogenetic role of chronic HBV infection remains to be proven.

Gene expression of the renin-angiotensin system in human kidney.

BACKGROUND: Immunocytochemical studies have revealed that all components of the renin-angiotensin system are widely distributed in human tissues yet the information on the gene expression of the renin-angiotensin system in various types of cell remains scarce. OBJECTIVE: We explored the presence of a local renin-angiotensin system in human kidney. METHODS: We sought to determine the presence of messenger RNA (mRNA) encoding for renin, angiotensinogen, and angiotensin converting enzyme (ACE) in cultured human glomerular cells and human umbilical vein endothelial cells using a two-step polymerase chain reaction. The gene expression of the renin-angiotensin system in normal human kidney and in diseased kidney was studied by in-situ hybridization using synthetic oligonucleotides. RESULTS: By using a two-step polymerase chain reaction, renin, angiotensinogen, and ACE mRNA were found in cultured mesangial and epithelial cells but only ACE mRNA was present in human umbilical vein endothelial cells. Renin mRNA was detected in juxtaglomerular granular cells and also in glomerular and tubular epithelia in normal kidney by in-situ hybridization. A similar tubular, but not mesangial, distribution was found with angiotensinogen and ACE mRNA. In contrast, stronger signals for renin, angiotensinogen and ACE mRNA were detected in mesangial and epithelial cells of kidney tissues from hypertensive patients and from patients with renal pathology characterized by mesangial proliferation (immunoglobulin A nephropathy, diabetes mellitus, or lupus nephritis). CONCLUSIONS: That gene expression of the renin-angiotensin system occurs in resident glomerular cells supports the hypothesis that there is a local renin-angiotensin system in human kidney. Our findings support the previous speculation that the renin-angiotensin system could be a local factor involved in the progression of chronic renal failure and consequent development of hypertension.

Antihypertensive agents: angiotensin converting enzyme inhibitors. 1-[3-(Acylthio)-3-aroylpropionyl]-L-prolines.

A series of 1-[3-(acylthio)-3-aroylpropionyl]-L-proline derivatives was synthesized. A number of these compounds are potent angiotensin converting enzyme (ACE) inhibitors that lowered blood pressure in aorta-coarcted renal hypertensive rats. The most active derivatives are 1-[3(R)-(acetylthio) -3-substituted-benzoyl)-2(S)-methyl-propionyl]-L-prolines with an in vivo activity equivalent to SQ 14,225 (captopril). Structure-activity relationships are discussed. Changes in the configuration of the alpha-methyl group and the S-acetyl group affect the ACE activity. Coupling of 3-(substituted-benzoyl)-2-methylpropionic acids to L-proline via enol lactones is described.

Coexistence of Kaposi's sarcoma and tuberculosis in a renal transplant recipient.

BACKGROUND: We describe a case of Kaposi's sarcoma that developed in a renal transplant recipient as early as 5 months after the transplant. METHOD: The Kaposi's sarcoma evolved in an aggressive manner, involving the oral mucosa, the cervical and mediastinal lymph nodes, the gastrointestinal tract, and possibly the lung. Histological features of tuberculosis were also detected incidentally on an excisional biopsy of the lymph node. The patient was given 12 months of antituberculous chemotherapy. At the same time, immunosuppression was gradually tapered over a 2- to 3-week period. RESULTS: Despite the aggressive nature of the disease, the Kaposi's sarcoma regressed completely without the institution of chemotherapy. The patient remained disease-free after a follow-up period of 30 months. The kidney allograft, however, was rejected and the patient required dialysis again. CONCLUSION: Although lymphadenopathy is a well-recognized feature in organ transplant recipients who develop Kaposi's sarcoma, one has to watch out for other coexisting diseases, such as tuberculosis, lymphoma, and cytomegalovirus infection.

Differential expression of a stress-modulating gene, BRE, in the adrenal gland, in adrenal neoplasia, and in abnormal adrenal tissues.

Genes that modulate the action of hormones and cytokines play a critical role in stress response, survival, and in growth and differentiation of cells. Many of these biological response modifiers are responsible for various pathological conditions, including inflammation, infection, cachexia, aging, genetic disorders, and cancer. We have previously identified a new gene, BRE, that is responsive to DNA damage and retinoic acid. Using multiple-tissue dot-blotting and Northern blotting, BRE was recently found to be strongly expressed in adrenal cortex and medulla, in testis, and in pancreas, whereas low expression was found in the thyroid, thymus, small intestine and stomach. In situ hybridization and immunohistochemical staining indicated that BRE was strongly expressed in the zona glomerulosa of the adrenal cortex, which synthesizes and secretes the mineralocorticoid hormones. It is also highly expressed in the glial and neuronal cells of the brain and in the round spermatids, Sertoli cells, and Leydig cells of the testis, all of which are associated with steroid hormones and/or TNF synthesis. However, BRE expression was downregulated in human adrenal adenoma and pheochromocytoma, whereas its expression was enhanced in abnormal adrenal tissues of rats chronically treated with nitrate or nitrite. These data, taken together, indicate that the expression of BRE is apparently associated with steroids and/or TNF production and the regulation of endocrine functions. BRE may play an important role in the endocrine and immune system, such as the cytokine-endocrine interaction of the adrenal gland.

Brain and vascular monoamine oxidase activity in the deoxycorticosterone-salt hypertensive rat.

1 The role of monoamine oxidase (MAO) in the maintenance of deoxycorticosterone-sodium chloride (DOCA-salt) hypertension was investigated by assaying the MAO activity both in central as well as peripheral blood vessels and in brain tissue. 2 The results suggest that the activity of MAO in the DOCA-salt hypertensive rat is similar to the activity present in the normotensive rat.

Studies on the effects of viprostol in isolated small blood vessels and thoracic aorta of the rat.

1. The effects of viprostol, prostaglandin E2 (PGE2) and nitroglycerin were studied in basilar artery, small mesenteric artery and the vein parallel to it as well as thoracic aorta of the rat. 2. In KCl-contracted basilar artery, viprostol produced a concentration-related biphasic response, contraction at concentrations less than 3 X 10(-6) M and relaxation at concentrations greater than 3 X 10(-6) M. PGE2 produced a concentration-related contraction while nitroglycerin produced a concentration-related relaxation. 3. In KCl-contracted small mesenteric artery, viprostol produced a biphasic response which was similar to that in the basilar artery. PGE2 produced a contraction and nitroglycerin produced relaxation in a concentration-dependent manner. 4. In KCl-contracted small mesenteric vein, in contrast to basilar and mesenteric artery, viprostol produced only a concentration-related relaxation in the range of 1 X 10(-6) to 1 X 10(-4) M. PGE2 produced a contraction and nitroglycerin produced a concentration-related relaxation. 5. In KCl-contracted thoracic aorta, PGE2 produced a biphasic response, relaxation at concentrations less than 3 X 10(-7) M and a concentration-related contraction at concentrations greater than 3 X 10(-7) M. Viprostol only produced a concentration-related contraction at concentrations greater than 1 X 10(-6) M, which was significantly less in magnitude than the contraction produced by PGE2. Nitroglycerin produced a concentration-related relaxation as seen in the small vessels. 6. In conclusion, the present data demonstrate that viprostol is a vasorelaxant agent which effectively dilates KCl-contracted basilar, small mesenteric artery and vein, but not the thoracic aorta of rat. The potent antihypertensive action of viprostol is probably due to its relaxant effect on the small arteries and veins but not on the large conduit artery.

A comparison of cardiac reactivity and beta-adrenoceptor number and affinity between aorta-coarcted hypertensive and normotensive rats.

1 The effects of noradrenaline (NA) and isoprenaline on isolated atria from aorta-coarcted hypertensive rats (AHR) at early (6 day) and chronic (28 day) stages of hypertension were studied and compared with time-matched, sham-operated, normotensive rats (SNR). The number and affinity of beta-adrenoceptor ((-)-[3H]-dihydroalprenolol binding sites) were also studied in cardiac membranes prepared from these animals. 2 Six and 28 days after complete ligation of the abdominal aorta between the two renal arteries, rats became hypertensive with significantly greater arterial blood pressures than time-matched SNR. 3 At both stages of hypertension, the atrial inotropic or chronotropic effects of NA and isoprenaline from hypertensive rats were similar to time-matched SNR. Moreover, no differences in atrial reactivity were observed between the early and chronic stages of hypertension. 4 Irrespective of the stage of hypertension, cardiac membranes from the AHR contained the same number of beta-adrenoceptors as time-matched SNR. In addition, the receptor affinity for the radioligand within each group was equivalent. However, the chronic stage hypertensive rats and their time-matched controls contained fewer beta-adrenoceptors and these receptors had greater affinity for the radioligand when compared with cardiac membranes from rats at the early stage of hypertension and their controls. 5 The observed equivalent chronotropic and inotropic responses to NA and isoprenaline between the hypertensive and normotensive rats in both stages of hypertension may be explained in terms of similar receptor number and receptor binding affinity. 6 The reduced number of beta-adrenoceptors with greater binding affinity in day 28 normotensive or hypertensive rats may be a compensatory mechanism for these animals to maintain normal cardiac function with increasing age.

Aortic vascular and atrial responses to (+/-)-1-O-octadecyl-2-acetyl-glyceryl-3-phosphorylcholine.

The effects of (+/-)-1-O-octadecyl-2-acetyl-glyceryl-3-phosphorylcholine (octadecyl-AGPC) were studied in three types of aortic vascular smooth muscle preparations, namely, strips, rubbed and unrubbed rings, and an atrial preparation in normotensive rats. In the resting tension state, octadecyl-AGPC did not elicit significant contractions in either rubbed or unrubbed ring preparations at concentrations lower than 1 X 10(-4) M. However, at a concentration of 3 X 10(-4) M, octadecyl-AGPC markedly contracted both types of ring preparations. This contractile response was partially antagonized by pretreatment with reserpine and completely blocked by phentolamine (1 X 10(-6) M). In preparations contracted with noradrenaline (NA), octadecyl-AGPC elicited biphasic responses in intact ring preparations; an initial relaxation followed by contraction. Octadecyl-AGPC induced only a slight contraction in strips and a slight relaxation in the rubbed ring preparation. Octadecyl-AGPC did not elicit any significant effect on chronotropy or inotropy at concentrations up to 3 X 10(-5) M. When the concentration was 1 X 10(-4) M, octadecyl-AGPC produced significant positive chronotropic and inotropic effects on spontaneously beating right and electrically driven left atrial preparations, respectively. Both effects were blocked by propranolol (5 X 10(-8) M); reserpine pretreatment antagonized only the chronotropic response. In [3H]-dihydroalprenolol [( 3H]-DHA) binding studies, octadecyl-AGPC had a Kd of 427.85 microM and thus was much less potent than isoprenaline (Kd = 465.10 nM) or propranolol (Kd = 4.4 nM) in displacing [3H]-DHA in rat cardiac membrane preparations. 6 In conclusion, relaxation and contraction induced by octadecyl-AGPC in aortic preparations is an indirect rather than a direct effect. An unknown factor released from endothelial cells is responsible for aortic smooth muscle relaxation by octadecyl-AGPC while released NA appears to be responsible for aortic vascular contraction and for the positive chronotropic and inotropic effects in the atrial preparations.

Evidence for the lack of interaction between (+/-)-1-O-octadecyl-2-acetylglyceryl-3-phosphorylcholine and alpha-adrenoceptors in vivo and in vitro.

The interactions of (+/-)-1-O-octadecyl-2-acetylglyceryl-3-phosphorylcholine (octadecyl-AGPC) with alpha-adrenoceptors were studied in rat mesenteric artery, cat nictitating membrane and on the blood pressure of the cat and spontaneously hypertensive (SH) rat. Using a direct radioligand alpha-adrenoceptor binding assay in particulate fractions of rat mesenteric arteries, octadecyl-AGPC was found to be 5 X 10(7) and 75 times less potent than prazosin and noradrenaline (NA), respectively, in displacing (2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxane ([3H]-WB 4101--a selective probe for the identification of alpha-adrenoceptors). In the cat, intravenous infusions of octadecyl-AGPC, which produce a hypotensive response, did not attenuate nictitating membrane contractions in vivo in response to intravenous injections of NA, adrenaline (Ad) or to electrical stimulation of the postganglionic fibres of the superior cervical ganglion. In these experiments, the pressor responses to NA or Ad were not affected by octadecyl-AGPC. Phentolamine, on the other hand, attenuated nictitating membrane contractions and blood pressure responses to Ad or NA. In the SH rat, octadecyl-AGPC decreased mean arterial blood pressure (MABP). After an intravenous dose of phentolamine which lowered MABP, the depressor response to octadecyl-AGPC was reduced. When MABP in the phentolamine-treated SH rat was restored to its initial level with an infusion of angiotensin II (AII), the depressor response to octadecyl-AGPC was restored to its original magnitude. The effectiveness of alpha-adrenoceptor blockade under these experimental conditions was monitored with intravenous NA and Ad. Thus, based on radioligand binding studies and pharmacological studies, it is concluded that octadecyl-AGPC lacks the ability to interact with alpha-adrenoceptors.

In vitro studies of aquaporins 1 and 3 expression in cultured human proximal tubular cells: upregulation by transferrin but not albumin.

Dysregulated renal water handling is a cardinal feature of nephrotic syndrome that has been shown in animal models of experimental nephrosis to mediate renal aquaporin (AQP) expression. However, data on the effect of proteinuria on the proximal tubule, which is heavily vested with AQP1 and therefore may participate in water homeostasis, are limited. To investigate this, we exposed primary human proximal tubular epithelial cells (PTECs) to two key proteinuric components shown to perturb tubule function: human serum albumin and transferrin. Using reverse-transcriptase polymerase chain reaction and immunocytochemical techniques, PTECs in the quiescent state were found to express AQP3 in addition to AQP1 gene and protein, which was also validated in a human proximal tubule cell line, HK-2. Immunohistochemical staining localized AQP1 synthesis to the apical and basolateral membranes and AQP3 synthesis to the basolateral membrane of proximal tubule epithelium. Transferrin in doses reaching nephrotic range upregulated PTEC transcription and translation of both AQP1 and AQP3 in a time- and dose-dependent manner. After 24 hours of stimulation, transferrin led to a 2.4- and 2.2-fold increase in AQP1 and APQ3 messenger RNA expression, whereas protein synthesis surged by 40.7% +/- 2.48% and 24.2% +/- 0.9% compared with control, respectively. These effects were not observed with albumin challenge and were not caused by osmolality fluctuation with transferrin treatment. In summary, our novel finding of AQP3 in PTECs indicates a role for AQP3 in proximal tubule water reabsorption. The pathophysiological significance of heightened AQP1 and AQP3 expression in PTECs on protein challenge as occurs in the nephrotic state requires further investigation.

Recurrent IgA nephropathy in renal transplant allografts.

Previous reports of renal transplantation for patients with underlying immunoglobulin A (IgA) nephropathy suggested a recurrence rate greater than 50% for transplant IgA nephropathy. Initially regarded as a benign condition, more recent data showed that recurrent transplant IgA nephropathy may be a significant contributor to graft loss. We performed a retrospective analysis in a single center of 48 kidney transplant recipients, all of Chinese origin, with biopsy-proven IgA nephropathy as the cause of end-stage renal failure to determine the recurrence rate of IgA nephropathy in the transplant allograft and subsequent clinical course in Chinese patients. Median duration of follow-up was 52 months (range, 18 to 155 months). Fourteen patients (29%) had biopsy-confirmed recurrent transplant IgA nephropathy after a median of 52 months (interquartile range, 23 to 82 months) posttransplantation. Recurrent transplant IgA nephropathy was associated with greater serum IgA levels (P = 0.01). The presence of HLA-A2 in transplant recipients (P = 0.002) appeared to protect them from developing recurrent IgA nephropathy in the transplant allograft. Twenty-nine percent of patients with recurrent transplant IgA nephropathy had progressive deterioration of graft function. The progressive graft dysfunction (GD) rate was greater in patients with a transplant from a living related donor (LRD; 21%) compared with those with a transplant from a cadaveric or living unrelated donor (URD; 3%; P = 0.062). Although the cumulative graft survival rate was 100% at 5 years for transplants from both LRDs and URDs, the 10-year graft survival rate was only 63% for a graft from an LRD versus 93% for a URD (log-rank test, P = 0.19). A review of other reported series of recurrent transplant IgA nephropathy also showed an apparently greater incidence of GD for a graft from an LRD (28%) compared with a URD (15%). Our data suggest that although recurrent transplant IgA nephropathy is highly prevalent among the Chinese population, the risk for disease recurrence is not particularly increased compared with other ethnic groups. The trend toward a greater risk for GD for living related compared with unrelated allografts in patients with IgA nephropathy needs to be confirmed with further prospective study.

Reversible renal failure in paroxysmal nocturnal hemoglobinuria.

A Chinese patient with paroxysmal nocturnal hemoglobinuria (PNH) developed acute nonoliguric renal failure with intercurrent urinary tract infection and hemolysis. There was no evidence of renal vein thrombosis. Renal biopsy showed features of acute tubular necrosis (ATN) and hemosiderosis. Magnetic resonance imaging (MRI) showed characteristic features of renal hemosiderosis. The patient was stabilized with temporary hemodialysis and intravenous fluid. The renal function fully recovered 3 weeks later. We review the literature and summarize the clinical features of this disease entity. To our knowledge, this case is the first to report such disorder with thorough investigation including concomitant diagnostic MRI imaging and renal biopsy.

Effective treatment of high-grade lymphoproliferative disorder after renal transplantation using autologous lymphocyte activated killer cell therapy.

Posttransplantation lymphoproliferative disorders (PTLD) is not uncommon and can occur in 2% to 5% of solid organ recipients on immunosuppression. Epstein-Barr virus (EBV) infection or reactivation and intensive anti-T lymphocyte treatment are important pathogenetic factors for a large proportion of these disorders. Nonclonal lesions with polymorphous histology have a potential for regressing when the immunosuppressants are reduced or stopped. Clonal tumors with a monomorphous histology carry a poor prognosis, and the mortality rate for monoclonal lymphoma has been reported as high as 80%. We report a renal transplant recipient who developed high-grade monoclonal lymphoma only 4 months after a live-donor transplantation. The tumor was EBV positive. Reduction of immunosuppressants resulted in minimal regression of the tumor. The patient was treated with adoptive immunotherapy using ex vivo generation of autologous lymphocyte activated killer (LAK) cells. She had leukapheresis, and autologous peripheral blood mononuclear cells were obtained and cultured in interleukin-2 (IL-2)-rich medium for 9 to 10 days. The IL-2-activated LAK cells were reinfused into the patient without any systemic administration of IL-2. The patient experienced no side effects during the infusion. There was no rejection episode, and the renal function of the patient remained stable after treatment. Computed tomography scan performed 2 months after the infusion showed marked regression of the lesions in the liver and spleen. Five months later, magnetic resonance imaging showed complete resolution of the tumor lesions. Ultrasonography 13 months after the LAK cell infusion showed no lesion. The allograft function was not affected after treatment. Adoptive immunotherapy using IL-2-activated autologous LAK cells was effective in treating this renal transplant patient with EBV-positive high-grade lymphoma. The patient's kidney allograft functioned well without any rejection.

Outcome of IgA nephropathy in adults graded by chronic histological lesions.

This prognostic study of primary immunoglobulin A (IgA) nephropathy focused on chronic irreversible glomerular sclerosis and interstitial fibrosis, based on the premise that this disease is characterized by a protracted and, for many, progressive course. We used a chronicity-based histological grading system to assess the biopsy specimens of 126 adults with IgA nephropathy over a median follow-up of 10 years. Our grading system included a glomerular grading (GG) of 1 to 3 based on the extent of glomerular sclerosis, a tubulointerstitial grading (TIG) of 1 to 3 based on the degree of tubular loss or interstitial fibrosis, and the evaluation of hyaline arteriolosclerosis (HA). These three histological parameters were correlated with each other and with serum creatinine level, degree of proteinuria, and blood pressure at the time of renal biopsy. Univariate analysis showed that these three histological and three clinical parameters were significantly correlated with renal survival. By multivariate analysis using the Cox regression model, GG, serum creatinine level, and degree of proteinuria represented independent prognostic factors of renal survival. For a subset of patients at a relatively early stage of disease with a serum creatinine level less than 130 micromol/L at the time of biopsy, all three histological features and degree of proteinuria were significantly correlated with renal survival, and GG was the only independent prognostic factor for renal outcome. This study shows that glomerular sclerosis represents the most important prognostic factor in adult patients with primary IgA nephropathy and has a strong predictive value. Our chronicity-based histological grading system not only correlates well with the natural history of IgA nephropathy but is also reproducible and relatively simple to apply.

Acute renal failure in a patient with Rosai-Dorfman disease.

Acute renal failure developed in a 57-year-old woman who had Rosai-Dorfman disease diagnosed 1 year previously on a cervical lymph node. Organ imaging showed diffuse masses infiltrating both kidneys. The renal biopsy showed a lymphoplasmacytic and histiocytic process extensively replacing the parenchyma, which is in keeping with Rosai-Dorfman disease of the kidneys. However, the typical lymphophagocytic cells were lacking. This case illustrates that diagnosis of Rosai-Dorfman disease in renal biopsy can be very difficult, requiring both exclusion of many benign and malignant lesions and a high index of suspicion for this condition. In particular, lymphoma was excluded based on the mixed polyclonal composition of inflammatory cells and the absence of atypical lymphoid proliferation. The renal function partially recovered after a course of therapy combining VP-16 (etoposide) and dexamethasone and remained stable over 4-year follow-up. This report emphasizes the importance of early diagnosis and intervention to safeguard renal function in extensive Rosai-Dorfman disease.