Medication-prescribing patterns of primary care physicians in chronic kidney disease.

BACKGROUND: We investigated the medication-prescribing patterns of primary care physicians in chronic kidney disease (CKD). SUBJECTS AND METHODS: This cross-sectional study included 3,310 medical doctors who graduated from Jichi Medical University. The study instrument was a self-administered questionnaire to investigate their age group, specialty, workplace, existence of a dialysis center at workplace, and their prescription frequencies (high, moderate, low, very low) of the following agents--calcium (Ca) inhibitors, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor antagonist (ARBs), statins, anti-platelet agents, erythropoietin (Epo), AST-120, vitamin D, and sodium hydrogen carbonate (NaHCO(3)). RESULTS: From a total of 933 responses, 547 (61.0 %) medical doctors prescribed medication for CKD. The prescription frequencies of Ca inhibitors, ACEIs, and ARBs were high (>90 %, high + moderate), those of statins, anti-platelet agents, Epo, and AST-120 were moderate (90-50 %, high + moderate), and those of vitamin D and NaHCO(3) were low (<50 %, high + moderate). The primary care physician's specialty was significantly associated with their prescription frequency of Ca inhibitors (p < 0.01). Their workplace was significantly associated with their prescription frequency of ACEIs (p < 0.01), ARBs (p < 0.01), Epo (p < 0.01) and vitamin D (p < 0.01). The existence of a dialysis center at their workplace was significantly associated with their prescription frequency of Epo (p < 0.01), vitamin D (p < 0.01) and NaHCO(3) (p < 0.01). Their age was not associated with their prescription frequency of any agents. CONCLUSION: Antihypertensives were highly prescribed, and vitamin D and NaHCO(3) were less prescribed by primary care physicians for CKD. There were certain associations between the prescribing patterns of primary care physicians for CKD and their specialty, workplace and the existence of a dialysis center at their workplace.

Primary care physicians' own exercise habits influence exercise counseling for patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: The appropriate exercise counseling for chronic kidney disease (CKD) patients is crucial to improve their prognosis. There have been few studies about exercise counseling by primary care physicians for CKD patients. We investigated primary care physicians' exercise counseling practices for CKD patients, and the association of these physicians' own exercise habits with exercise counseling. METHODS: The population of this cross-sectional study was 3310 medical doctors who graduated from Jichi Medical University from 1978 to 2012. The study instrument was a self-administered questionnaire that was mailed in August 2012 to investigate their age class, specialty, workplace, exercise habits, and practices of exercise counseling for CKD. RESULTS: 581 (64.8%) medical doctors practiced the management of CKD among a total of 933 responses. These 581 medical doctors were defined as CKD primary care physicians and their answers were analyzed. CKD primary care physicians' own exercise habits (frequencies and intensities) were as follows: frequencies: daily, 71 (12.1%); ≥ 2-3 times/week, 154 (26.5%); ≥ 1 time/week, 146 (25.1%); and ≤ 1 time/month, 176 (30.2%); intensities: high (≥ 6 Mets), 175 (30.1%); moderate (4-6 Mets), 132 (22.7%); mild (3-4 Mets), 188 (32.3%); very mild (<3 Mets), 47 (8.1%); and none, 37 (6.4%). The CKD primary care physicians' exercise recommendation levels for CKD patients were as follows: high, 31 (5.3%); moderate, 176 (29.7%); low, 256 (44.0%); and none, 92 (15.8%). The CKD primary care physicians' exercise recommendations for CKD patients were significantly related to their own exercise frequency (p < 0.001), but they were not related to their age, specialty, workplace, or exercise intensity. CONCLUSIONS: CKD primary care physicians' exercise recommendation level for CKD patients was limited. In addition, CKD primary care physicians' own exercise habits influenced the exercise counseling for CKD patients. The establishment of guidelines for exercise by CKD patients and their dissemination among primary care physicians are needed.(University Hospital Medical Information Network Clinical Trial Registry. number, UMIN000011803. Registration date, Sep/19/2013).

A case of IgG4-related tubulointerstitial nephritis with left hydronephrosis after a remission of urinary tract tuberculosis.

IgG4-related systemic disease encompasses multi-organ disorders, including tubulointerstitial nephritis. This disease is accompanied by a high serum IgG4 concentration and IgG4-positive plasma cell infiltration. We herein describe a 63-year-old woman with renal failure and dryness of the eyes and mouth, who had been treated with antituberculosis agents for urinary tract tuberculosis. She had a negative finding for a PCR analysis for Mycobacterium tuberculosis, a positive QuantiFERON-TB test, high serum IgG4 concentrations (2,660 mg/dl), and low serum IgM and IgA concentrations (34 and 82 mg/dl, respectively). Imaging tests revealed swelling in the submandibular glands, pancreas, and right kidney. A renal biopsy showed IgG4-positive plasma cell infiltration in the interstitium and tubular atrophy. This case was diagnosed as IgG4-related systemic disease. Corticosteroid therapy improved renal failure and swelling in the submandibular glands, pancreas, and right kidney. The case suggests that an abnormal reaction to tuberculosis may be associated with a predominance of type-2 helper T-cell immunity, thus resulting in IgG4-related systemic disease.

ANCA-associated crescentic glomerulonephritis with immune complex deposits.

BACKGROUND: Several authors have reported cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis (CGN) with definite immune complex (IC) deposits, however, the clinical and pathological significance of IC deposits in patients with ANCA-associated CGN remains unclear. METHODS: Renal biopsy specimens from 28 patients with a diagnosis of CGN and positivity for anti-myeloperoxidase (MPO)-ANCA were retrospectively evaluated. Clinical data were compared between patients with IC deposits (Group A) and patients without IC deposits (Group B). RESULTS: In 12 patients (43%; Group A), IC deposits were detected in the mesangium and/or along the glomerular capillary walls, while typical pauci-immune CGN without IC deposits was found in 16 patients (57%; Group B). Compared with Group B, Group A had lower levels of MPO-ANCA (171 ± 156 vs. 352 ± 299 EU) and C-reactive protein (CRP) (0.63 ± 1.04 vs. 4.45 ± 4.00 mg/dl), as well as less pulmonary involvement (8.3% vs. 56.3%) at diagnosis. However, Group A had significantly heavier proteinuria (2.46 ± 1.67 vs. 0.76 ± 0.52 g/d). Group A was classified into three subgroups: Group A1 with mesangial IgA and C3 deposits, A2 with mesangial IgG and C3 deposits, and A3 with IgG and C3 deposits mainly in the capillary walls. CONCLUSIONS: ANCA-associated CGN causes two types of renal involvement, which are the pauci-immune type without IC deposits and the IC deposition type that involves three patterns of IC deposition in the glomeruli. The reason why IC deposits are associated with renal-limited vasculitis and not systemic vasculitis remains unclear.

Severe osteomalacia caused by short bowel syndrome in a patient on long-term hemodialysis after parathyroidectomy.

In January 2009, a 70-year-old Japanese woman on long-term dialysis was admitted to our hospital for evaluation of a painful left leg. Maintenance dialysis was started in 1982, and parathyroidectomy was performed for secondary hyperparathyroidism in 2004. Most of her small intestine was resected because of superior mesenteric artery thrombosis in 2006, and the remaining small bowel only extended 50 cm distal to the ligament of Treitz. Parenteral nutrition was started after bowel resection. Fracture of her left leg occurred suddenly without any precipitating factors in January 2009, and iliac bone biopsy revealed severe osteomalacia with an increase of total osteoid volume (57.6%) (>15%) and no fibrous tissue (0%) (<0.5%). Although phosphorus and active vitamin D were administered intravenously to correct her hypophosphatemia and vitamin D deficiency, significant improvement was not achieved. This case indicates that when a patient on long-term dialysis with parathyroidectomy also suffers from short bowel syndrome, osteomalacia may become very severe. Lack of healing of the fracture, persistence of pain, and subsequent fracture even after vigorous treatment for low serum phosphate and calcitriol levels implied that these medications were not necessarily sufficient for this patient.

Successful treatment of acute promyelocytic leukemia in a patient on hemodialysis.

Acute promyelocytic leukemia (APL) has the best prognosis among acute leukemias, but there is little data about APL in patients on hemodialysis. A 64-year-old hemodialysis patient was successfully treated for APL by induction therapy with all-trans retinoic acid (ATRA), three courses of consolidation therapy with Ara-C, mitomycin C (MIT), daunorubicin (DNR), and idarubicin (IDR), and maintenance therapy with ATRA. Complete remission has been maintained for 42 months in this patient. With dose modification, ATRA and chemotherapy may be safely given to patients on hemodialysis.

How to treat patients with systemic amyloid light chain amyloidosis? Comparison of high-dose melphalan, low-dose chemotherapy and no chemotherapy in patients with or without cardiac amyloidosis.

BACKGROUND: High-dose melphalan and autologous stem cell transplantation (HDM) is an effective treatment for systemic amyloid light chain (AL) amyloidosis but the eligibility criteria exclude many patients with this disorder. The aim of this study was to determine appropriate treatment strategies for systemic AL amyloidosis according to each patient's clinical condition in Japan. METHODS: Historical cohort study. Fifty-three patients with systemic AL amyloidosis (those with malignancies were excluded) were treated in our hospital with HDM (15 patients), melphalan + prednisolone (MP) (17 patients), vincristine + adriamycin + dexamethasone (VAD) (11 patients), or supportive treatment (no chemotherapy, 10 patients). We compared the survival rates among these treatment groups. RESULTS: Mean survival was significantly longer in the HDM group than in the other three groups (P < 0.01, log-rank test). This trend remained the same when patients were divided into those with and without cardiac amyloid involvement. Furthermore, in patients with heart involvement, survival in the VAD therapy group was significantly inferior to that in the MP therapy group (P < 0.01 by log-rank test). Significant factors related to the survival rate included the presence or absence of heart involvement and treatment modality. CONCLUSIONS: HDM should be considered the treatment of choice in eligible patients with systemic AL amyloidosis even in the presence of cardiac amyloidosis. If HDM is not eligible, indications for VAD therapy should be carefully evaluated in patients with cardiac amyloidosis.

Membranous nephropathy in an HIV-positive patient complicated with hepatitis B virus infection.

In ordinary settings, human immunodeficiency virus (HIV)-associated nephropathy should be considered when HIV infection is associated with heavy proteinuria. On the other hand, hepatitis B virus (HBV) may also play a role in the development of glomerular injury among patients with HIV infection, since HIV and HBV infections commonly occur together due to shared modes of transmission. We present here a case of nephrotic syndrome in an HIV-positive patient complicated with HBV infection. A renal biopsy revealed sparse granular deposits of immunoglobulin G in the subepithelial region, consistent with membranous nephropathy (MN) stage I. Moreover, immunostaining exhibited weak anti-hepatitis B core activity within glomeruli. These results led us to consider that HBV-associated MN might play a role in the development of nephrotic syndrome. Although anti-viral treatment for patients with HBV-associated MN has been suggested to be clinically effective, the use of two anti-HIV agents (tenofovir and emtricitabine), both of which have anti-HBV activities, was not effective for the patient's nephrotic syndrome, despite obtaining a decrease in the serum HBV-DNA levels. A lack of prospective data suggests that many decisions on the treatment of glomerulopathies with HIV infections are potentially empirical. Obviously, further studies and accumulated clinical experience are required to better determine the pathogenesis and management of HBV-associated MN among patients with HIV infections.

The renal cyst infection caused by Salmonella enteritidis in a patient with autosomal dominant polycystic kidney disease: how did this pathogen come into the renal cysts?

A 40-year-old Japanese man was admitted to our hospital for investigation of fever and right flank pain starting after watery diarrhea. Salmonella enteritidis was cultured from samples of stool and blood. Although his diarrhea subsided soon, high fever persisted and flank pain got worse. Magnetic resonance imaging (MRI) revealed four areas of abnormal intensity in renal cysts and computed tomography showed the same findings. Renal cysts infection was diagnosed. After ultrasound-guided aspiration of these cysts, his fever subsided. Culture of each aspirate grew Salmonella enteritidis. Although the route of cyst infection in ADPKD generally remains unclear, the clinical course of our patient may indicate that gastrointestinal tract infection progressed to renal cyst infection when bacteremia occurred due to bacterial translocation.

Characteristics of revascularization treatment for arteriosclerosis obliterans in patients with and without hemodialysis.

BACKGROUND: Limb ischemia is a major complication in patients who are receiving hemodialysis (HD). In this study, distinctive features and factors affecting the outcome of HD patients with limb ischemia are identified. METHODS AND RESULTS: One hundred and eighty consecutive symptomatic limb ischemic patients who were or were not receiving HD and who successfully underwent surgical bypass grafting (bypass, n=75) or endovascular angioplasty (percutaneous transluminal angioplasty (PTA), n=105) were retrospectively compared at our hospital. The endpoint of this study was amputation of the ischemic leg or death. Median follow up was 2.25 years. The amputation-free survival of HD patients was significantly lower than that of non-HD patients (P<0.0001). In the bypass group, the amputation-free survival of HD patients was significantly lower than that of non-HD patients (P=0.0002), even if the graft was patented or not (P=0.77). In contrast, in the PTA group, the amputation-free survival of HD patients was lower than that of non-HD patients (P=0.03), and with a significantly lower patency rate (P=0.0004). Predictors of amputation-free survival differed between HD and non-HD patients; predictors were diabetes mellitus and gender in HD patients, while they were Fontaine classification and hyperlipidemia in non-HD patients. The infectious death rate was higher in HD patients than in non-HD patients (53% vs 22%, P<0.05). CONCLUSIONS: This study clearly showed a poorer prognosis in HD patients than in non-HD patients especially after bypass surgery, even if the the graft was patented or not.

Long-term preserved renal function of a patient with mass-forming granulomatous interstitial nephritis by biopsy-based steroid therapy.

In 2001, a 41-year-old Japanese woman was referred to our hospital because of severe renal dysfunction and fever of unknown origin. On admission, her serum creatinine was 8.7 mg/dL, urine protein was 0.3 g/day, and urine ß(2)-microglobulin was 81,007 µg/day. Computed tomography (CT) scans showed bilateral contracted kidneys with a mass projecting from the lower pole of the right kidney. Biopsy of this lesion revealed interstitial nephritis and a noncaseating granuloma. Because extrarenal organ involvement or laboratory findings specific for sarcoidosis or other primary diseases were not detected, idiopathic granulomatous interstitial nephritis (GIN) was diagnosed. Prednisolone was started at dosage of 30 mg daily, and serum creatinine decreased to 5.5 mg/dL after 1 month. Her renal function was preserved for 8 years, but maintenance hemodialysis had to be started in 2009. A surgical specimen obtained after initiation of dialysis showed resolution of GIN in the renal mass lesion, which presumably resulted in preservation of renal function over the long term. Even in patients with severe renal dysfunction, histological diagnosis of GIN might lead to prognostic improvement because of appropriate therapeutic intervention.

Transarterial renal embolization for enlarged horseshoe kidney.

A 56-year-old Japanese man was admitted to our hospital with abdominal fullness in June 2006. He had been diagnosed as having a horseshoe kidney by computed tomography in January 2002. At that time, renal dysfunction (serum creatine: 2.0 mg/dl) was detected. Even after hemodialysis was started for end-stage renal failure in March 2006, his abdominal fullness became progressively worse. CT scanning showed a markedly enlarged horseshoe kidney. Transarterial embolization (TAE) was performed via the right renal arteries with 14 platinum microcoils; the left renal arteries were not embolized in order to preserve sufficient parenchyma and a urine volume of more than 1,000 ml daily. Two years after TAE, a decrease in the size of the left kidney was noted along with the right kidney. However, urine output was still more than 1,000 ml daily. It is possible that one kidney compressed the contralateral kidney, resulting in enlargement of both components of the horseshoe kidney and renal dysfunction. TAE may be a useful option for obstructive uropathy in patients with horseshoe kidney, which has conventionally been treated surgically.

AL amyloidosis with IgD-lambda monoclonal gammopathy and lambda-type Bence-Jones protein: successful treatment by autologous stem cell transplantation.

A 45-year-old Japanese woman had been diagnosed with monoclonal gammopathy of undetermined significance (MGUS) featuring urinary Bence-Jones protein of the lambda type (BJP-lambda) for 11 years. She then developed eyelid purpura, dyspnea, and flank pain. Abdominal CT scans revealed renal infarction. Biopsy of the kidney, heart, jejunum, and skin demonstrated amyloid deposits in the vessel walls, but not in the glomeruli. She was diagnosed as having AL amyloidosis with IgD-lambda monoclonal gammopathy and BJP-lambda. Autologous stem cell transplantation (SCT) was done after chemotherapy with vincristine, daunorubicin, dexamethasone (VAD), and high-dose melphalan (HDM). This reduced the IgD level from 156 to 0.1 mg/dL, along with the disappearance of BJP, despite cerebral infarction during chemotherapy. We recommend SCT for patients with IgD-associated AL amyloidosis.

Development of myeloperoxidase-antineutrophil cytoplasmic antibody-associated renal vasculitis in a patient receiving treatment with anti-tumor necrosis factor-α.

We report on a 33-year-old woman who presented with positive myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) during rheumatoid arthritis treatment with infliximab. She had a history of worsening arthralgia, and urinalysis showed the new occurrence of hematuria and proteinuria. Renal biopsy showed necrotizing crescentic glomerulonephritis. Immunosuppressive therapy and discontinuation of the infliximab therapy alleviated her arthralgia and improved the urinalysis results. We report this rare case in which an anti-tumor necrosis factor-α (TNF-α) agent for ANCA-associated systemic vasculitis was studied.

A case of primary hyperparathyroidism with severe bone and renal changes.

We report a 79-year-old Japanese woman who had primary hyperparathyroidism (HPT) with end-stage renal disease and severe bone changes. In 2004, she began to experience pain in her shoulders and knees, as well as muscle weakness and anorexia. She already had renal failure with a serum Cr of 4.7 mg/dl, while serum calcium was 9.6 mg/dl, PTH was 2,710 pg/ml, and serum alkaline phosphatase was 923 mU/ml. Multiple fractures of the pelvic bones and lumbar spine, osteoporosis, and subperiosteal bone resorption were detected. Although hemodialysis (HD) was started in February 2005, her symptoms became more severe. Total parathyroidectomy (PTX) and right iliac crest bone biopsy were performed. Histomorphometric analysis of the cancellous bone indicated a diagnosis of osteitis fibrosa, but a reduction of cortical bone and near absence of cancellous bone were also apparent. This showed that bone resorption by osteoclasts was predominant over bone formation by osteoblasts. Soon after PTX, her pain subsided completely. We conclude that primary HPT should be detected and treated early enough to avoid renal damage, since renal dysfunction markedly accelerates bone changes in patients with primary HPT.

Infected hepatic and renal cysts: differential impact on outcome in autosomal dominant polycystic kidney disease.

BACKGROUND: Infected cysts are a frequent and serious complication of autosomal dominant polycystic kidney disease. Such infections are classified into those affecting hepatic cysts and those affecting renal cysts. The purpose of this study was to compare the clinical course of infected hepatic cysts with that of infected renal cysts in patients with autosomal dominant polycystic kidney disease. METHODS: We analyzed 43 patients referred to us for additional treatment of severely infected cysts between January 2004 and December 2006. All patients who required further treatment in addition to antibiotic therapy were included. RESULTS: Aspiration was performed in all 28 patients with infected hepatic cysts. As a result, 17 patients were cured, 4 remain under treatment, and 6 died. One patient was cured by partial hepatectomy. Among the 15 patients with renal cysts, aspiration was performed in 4 with identifiable infected cysts, while renal transcatheter arterial embolization after appropriate antibiotic therapy was performed in 11 without identifiable infected cysts. No patient developed recurrence. CONCLUSION: In patients with infected renal cysts, aspiration or renal transcatheter arterial embolization after appropriate antibiotic therapy was effective. Although aspiration was often effective in patients with infected hepatic cysts, a good outcome was less likely than in those with renal cysts.

Plasma adiponectin: a predictor of coronary heart disease in hemodialysis patients--a Japanese prospective eight-year study.

BACKGROUND/AIM: Plasma adiponectin may play a protective role in the pathogenesis of cardiovascular disease in hemodialysis (HD) patients. We examined the effect of plasma adiponectin levels on the prognosis of the HD patients. METHODS: 68 HD patients (male:female = 38:30) were subjected to plasma adiponectin measurement in 1998 and followed up over 8 years. RESULTS: Plasma adiponectin concentrations differed between male and female patients (9.3 vs. 15.7 microg/ml). The plasma adiponectin concentration as a whole was positively correlated with serum high-density lipoprotein cholesterol and negatively with serum creatinine and waist circumference. During an 8-year follow-up, the cardiac events occurred in 7 of 38 men and in 10 of 30 women. Cox's proportional hazard model analysis in a stepwise manner revealed that coronary heart disease (CHD) was associated with intact parathyroid hormone concentration, age, and the presence of diabetes in men whereas plasma adiponectin concentration was the most powerful single predictor in women. The impact of the plasma adiponectin concentration was strengthened by Kaplan-Meier survival analysis. In the group with a lower plasma adiponectin concentration, CHD events were significantly increased in men (p = 0.043) and in women (p = 0.007). CONCLUSION: Plasma adiponectin concentration may predict CHD outcomes in HD patients.

Successful treatment of primary AL amyloidosis by VAD therapy, high-dose melphalan, and autologous peripheral stem cell transplantation.

We report a 58-year-old Japanese man with primary systemic AL amyloidosis who achieved disappearance of proteinuria including Bence-Jones protein (lambda-type) after two courses of VAD therapy (vincristine, doxorubicin, and dexamethasone) and subsequent high-dose melphalan, followed by autologous peripheral blood stem cell transplantation. Because this patient did not have any apparent amyloidosis-related heart or liver damage and met all of the eligibility criteria for this therapy, this treatment was performed. Both proteinuria and M-protein disappeared completely, and he is doing well clinically at 19 months after treatment. However, amyloid deposits were still found in the kidneys, including the glomeruli and tubulointerstitium, when renal biopsy was done at 8 months after treatment. In the future, we may reach a time when clinical remission corresponds to histological remission.

Percutaneous transcatheter hepatic artery embolization for liver cysts in autosomal dominant polycystic kidney disease.

BACKGROUND: We have achieved renal contraction therapy in patients with autosomal dominant polycystic kidney disease (ADPKD) by means of renal transcatheter arterial embolization (TAE) using intravascular coils, decreasing renal size and improving quality of life in almost all patients. We presently perform hepatic TAE in patients with intractable symptomatic polycystic liver. STUDY DESIGN: Uncontrolled trial. SETTING & PARTICIPANTS: 30 patients with ADPKD referred for arteriography to an academic medical center. 22 patients had kidney failure treated by means of dialysis. INTERVENTION: We embolized arteries supplying hepatic segments replaced by cysts that were associated with well-developed hepatic arteries, but obstructed intrahepatic portal veins. OUTCOMES & MEASUREMENTS: Various volumes before and after TAE were compared by using computed tomography and National Institutes of Health Image software in 30 patients with follow-up computed tomography 18 to 37 months after therapy. RESULTS: Total liver volume and total intrahepatic cyst volume decreased from 7,882 +/- 2,916 and 6,677 +/- 2,978 to 6,041 +/- 2,282 and 4,625 +/- 2,299 cm(3), respectively (P < 0.0001 for both). Fractions of remaining (FR) total liver volume and FR of intrahepatic cyst volume were 78.8% +/- 17.6% and 70.4% +/- 20.9%, respectively. Hepatic parenchyma increased from 1,205 +/- 250 to 1,406 +/- 277 cm(3) (P = 0.0004). In 29 of 30 patients, both total liver volume and intrahepatic cyst volume decreased; in 1 patient, total liver volume increased from 5,755 to 7,069 cm(3), whereas cysts enlarged from 4,500 to 5,531 cm(3). No serious complications were experienced. In 24 patients, the post-TAE course was favorable. TAE failed to benefit 6 patients because of unrelated hepatic infection, peritonitis, hepatic failure, acute leukemia, or pelvic fracture. LIMITATIONS: Absence of a control group. CONCLUSIONS: TAE may be an option for patients with ADPKD with symptomatic polycystic liver who are not candidates for surgical treatment.

Induction of anti-carbonic-anhydrase-II antibody causes renal tubular acidosis in a mouse model of Sjogren's syndrome.

BACKGROUND/AIM: We recently reported that renal tubular acidosis (RTA) in Sjogren's syndrome (SjS) is associated with high titers of an autoantibody against carbonic anhydrase (CA) II, an important enzyme in renal acid-base regulation. The purpose of this study was to determine whether a CA-II antibody could cause RTA in a mouse model of SjS. METHODS: PL/J mice were immunized with human CA II to induce CA II antibody formation, whereas controls were injected with phosphate-buffered saline and adjuvant. After 6 weeks, anti-CA-II antibody titers were measured, then ammonium chloride was administered orally for 1 week to detect any acidification defect. RESULTS: CA-II-immunized mice showed higher anti-CA-II antibody titers than control mice. Pathologically, lymphocytic and plasma cell infiltration was seen in the salivary glands and kidneys of CA-II-immunized mice, but not in controls. On acid loading, blood pH and urine pH decreased in both groups of mice, but the slope of urine pH versus blood pH was less steep in the CA-II-immunized mice, suggesting that these mice had an impaired ability to reduce their urine pH in the face of metabolic acidosis. CONCLUSION: CA-II-immunized mice had a urinary acidification defect, which may be similar to that seen in patients with SjS.