Relapse during and after regular single-dose rituximab treatment in adult patients with steroid-dependent nephrotic syndrome.

BACKGROUND: Rituximab is widely used in patients with steroid-dependent nephrotic syndrome. However, information on the effect of long-term rituximab treatment is limited. This study examined the efficacy of rituximab during and after treatment in adult patients with steroid-dependent nephrotic syndrome. METHODS: This retrospective cohort study included 30 patients with steroid-dependent nephrotic syndrome. Patients received regular single-dose rituximab (500 mg) intravenously every 6 months. Discontinuation of rituximab was considered after four to six doses if there was no recurrence of nephrotic syndrome. Glucocorticoid discontinuation with remission, first relapse after rituximab initiation, and relapse after regular rituximab treatment discontinuation were evaluated. RESULTS: The median age was 38 (range 18-67) years. Of 30 patients, 13 and 17 were men and women, respectively. Prior to rituximab treatment, the median number of nephrotic syndrome relapses in the patients was 5 (range 2- > 20). The 1 year discontinuation rate of glucocorticoids with remission was 83%. All patients discontinued glucocorticoid treatment at least once until 3 years and 7 months. The 1 and 2 year relapse rates after initiation of rituximab treatment were 0% and 3%, respectively. 25 patients discontinued regular rituximab treatment after a median number of six (4-12) doses. Six patients relapsed after discontinuing rituximab, and the 1 and 2 year relapse rates after the last regular rituximab treatment were 9% and 25%, respectively. CONCLUSION: All patients with steroid-dependent nephrotic syndrome who received rituximab could discontinue glucocorticoid treatment with remission, and three-fourths of the patients remained in remission for > 2 years after discontinuing rituximab treatment.

Association of Familial Fanconi Syndrome with a Novel GATM Variant.

Fanconi syndrome is a disorder of the proximal renal tubule. Recently, advanced genetic analysis technology has revealed that several genes cause familial Fanconi syndrome. We identified a family with autosomal dominant Fanconi syndrome and chronic kidney disease with a novel glycine amidinotransferase (GATM) variant. Case 1 was a 57-year-old Japanese woman. Her father and two siblings had Fanconi syndrome or chronic kidney disease. She presented to our hospital at the age of 34 years with recurrent glucosuria. Her height and weight were 151 cm and 46.6 kg, respectively. Laboratory tests showed glucosuria, hypophosphatemia, hypouricemia, and normal renal function. Her serum creatinine level gradually increased over the following next two decades, and she developed end-stage renal disease. Case 2, the daughter of Case 1, was a 26-year-old woman. Her height and weight were 151 cm and 37.5 kg, respectively. Glucosuria was detected at the age of 13 years, which led to a referral to our hospital. Urinalysis showed low-molecular-weight proteinuria. She was diagnosed with Fanconi syndrome. At the age of 26 years, she had glucosuria, low-molecular-weight proteinuria, hypouricemia, and normal renal function. Genetic testing of both cases revealed a novel missense variant in GATM. The heterozygous missense variants in GATM have been reported to cause familial Fanconi syndrome, which manifests early in life and progresses to renal glomerular failure by mid-adulthood. The novel GATM variant detected in our cases was suspected to be associated with the development of Fanconi syndrome. GATM variants should be tested in patients with idiopathic Fanconi syndrome.

Renal injury associated with MYH9 disorder with 5773delG mutation: A case report.

A 35-year-old man with persistent urine abnormalities and renal dysfunction was referred to our hospital. May-Hegglin anomaly was suspected, and a renal biopsy showed focal segmental glomerulosclerosis (FSGS) with IgA deposition. Electron microscopy revealed foot process effacements and intense bleb-like morphological changes in podocytes. Nonmuscle myosin heavy chain IIA (NMMHCIIA) staining of granulocytes revealed a localized, type II pattern, and genomic DNA sequencing of MYH9 exon 40 revealed MYH9 5773delG mutation (c.5773delG [p.(Asp1925Thrfs*23)]). Podocytes were significantly stained by an antibody specific for NMMHC-IIA abnormalities associated with this mutation. Colocalization observation of vimentin and NMMHC-IIA demonstrated a diminished form of NMMHC-IIA in podocytes. Taking these observations into account, it was determined that the present case was likely associated with MYH9 disorder. Treatment was started with olmesartan, followed by methylprednisolone pulse therapy 3 times bi-monthly. Finally, the patient began hemodialysis 18 months later. This is the first known report of renal phenotype expression associated with this MYH9 mutation. FSGS can occur in association with MYH9 mutations at the 3' regions, such as exon 40. Abnormal expression or metabolism of NMMHC-IIA in podocytes might be related to the formation of FSGS lesions due to this MYH9 mutation.

Chemoprophylaxis against Pneumocystis jirovecii pneumonia in Japanese patients with ANCA-associated vasculitis: An observational study.

OBJECTIVES: This study investigated the current practice of prophylactic treatment against Pneumocystis jirovecii pneumonia (PCP) and its effectiveness in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: This study included 319 patients registered from 53 institutions in Japan and newly diagnosed with AAV. During the 2-year observation period, we examined the frequency of usage, effectiveness and safety of prophylactic drugs against PCP. RESULTS: Most patients received prophylactic drugs against PCP with the initiation of immunosuppressive agents, and >50% of them remained on chemoprophylaxis against PCP at 2 years after. The initial daily dose of oral prednisolone and the proportion of cyclophosphamide administration were higher in patients who received chemoprophylaxis against PCP than in those who did not. PCP occurred in nine patients (3%) and resulted in the death of four. The incidence rate of PCP in patients who received chemoprophylaxis was 1.13/100 patient-years (95% confidence interval, 0.38-2.68) and that in those who did not was 2.74 (1.04-6.02). The incidence rate ratio was 0.41 (0.11-1.53). CONCLUSIONS: The markedly low incidence of PCP may be attributed to the continuous chemoprophylaxis against PCP received by >50% of Japanese patients with AAV, although the effectiveness of chemoprophylaxis against PCP was not statistically confirmed.

Damage control surgery for grade IV blunt hepatic injury with multiple organ damage in a child: a case report.

BACKGROUND: Intra-abdominal hemorrhage caused by blunt hepatic injury is a major cause of morbidity and mortality in patients with abdominal trauma. Some of these patients require laparotomy, and rapid decision-making and life-saving surgery are essential. Damage control (DC) surgery is useful for treating children in critical situations. We performed this technique to treat an 8-year-old boy with grade IV blunt hepatic injury and multiple organ damage. This is the first report of the use of the ABTHERA Open Abdomen Negative Pressure Therapy System (KCI, now part of 3 M Company, San Antonio, TX, USA) for DC surgery to rescue a patient without neurological sequelae. CASE PRESENTATION: An 8-year-old boy was brought to the emergency department of our hospital after being run over by a motor vehicle. He had grade IV blunt hepatic injury, thyroid injury, and bilateral hemopneumothorax. Although he was hemodynamically stable, the patient's altered level of consciousness, the presence of a sign of peritoneal irritation, and suspicion of intestinal injury led us to perform exploratory laparotomy. As part of a DC strategy, we performed gauze packing to control hemorrhage from the liver and covered the abdomen with an ABTHERA Open Abdomen Negative Pressure Therapy System to improve the patient's general condition. Eighteen days after admission, the patient was diagnosed with a biliary fistula, which improved with percutaneous and external drainage. He had no neurological sequelae and was discharged 102 days after injury. CONCLUSION: The DC strategy was effective in children with severe blunt hepatic injury. We opted to perform DC surgery because children have less hemodynamic reserve than adults, and we believe that using this strategy before the appearance of trauma triad of death could save lives and improve outcomes. During conservative management, it is important to adopt a multistage, flexible approach to achieve a good outcome.

Orthogonal antibody testing for COVID-19 among healthcare workers in a non-epidemic place and time:Japan's Iwate Prefecture, May 18-31, 2020.

Of the 47 prefectures in Japan, Iwate had the fewest cases of coronavirus disease 2019 (COVID-19), with the first diagnosis officially confirmed on July 28, 2020. A baseline serological survey of COVID-19 antibodies is essential to accurately evaluate an epidemic outbreak. The primary purpose of this study was to determine pre-epidemic prevalence of COVID-19 antibodies among healthcare workers, using two laboratory-based quantitative tests. In addition, a point-of-care (POC) qualitative test, rapid, simple, and convenient for primary care clinics, was compared with the laboratory-based tests. All antibody tests were performed on serum from 1,000 healthcare workers (mean age, 40 ± 11 years) in Iwate Prefectural Central Hospital, May 29-31, 2020. A COVID-19 case was defined as showing positive results in both laboratory-based quantitative tests. None of 1,000 samples had positive results in both of the laboratory immunoassays. The POC test showed positive results in 33 of 1,000 samples (3.3%) (95% confidence interval:2.19-4.41), but no samples were simultaneously positive in both laboratory-based tests. In conclusion, COVID-19 cases were not serologically confirmed by a baseline control study of healthcare workers at our hospital in late May, 2020. Moreover, the POC qualitative test may offer no advantage in areas with very low prevalence of COVID-19, due to higher false-positive reactions compared with laboratory-based quantitative immunoassays.

First case report of monoclonal IgG3-heavy-chain glomerulonephritis with microtubular structures.

Our patient was a 69-year-old woman admitted to our hospital for heavy proteinuria and hematuria. A renal biopsy showed findings similar to those of membranoproliferative glomerulonephritis associated with nodular lesions, and immunofluorescence showed marked deposits of IgG, C1q, and C3 on the peripheral capillary walls. IgG3 alone was observed on IgG subclass staining with no κ or λ light chains, and Congo red staining was negative. These findings suggested IgG3-heavy-chain deposition disease (HCDD). However, we did not find a deletion of the first heavy-chain constant domain, which is commonly observed in HCDD. Electron microscopy showed randomly arranged subendothelial microtubular structures with diameters of 70-90 nm. Altogether, the diagnosis of HCDD could not be made, although monoclonal IgG3 deposits in glomeruli were observed. This is the first case report of monoclonal IgG3-heavy-chain glomerulonephritis with subendothelial-based, randomly arranged microtubular structures with diameters of 70-90 nm.

Methylglyoxal as a prognostic factor in patients with chronic kidney disease.

AIM: Advanced glycation end products and their precursors cause vascular damage through oxidative stress. We investigated the hypothesis that methylglyoxal (MG), 3-deoxyglucosone (3-DG) and pentosidine influence outcomes of chronic kidney disease (CKD) patients. METHODS: We conducted a 3 years prospective observational study involving 150 outpatients at CKD stages 3-5. At enrolment, MG, 3-DG and pentosidine plasma concentrations were measured; patients were divided into tertiles according to the concentration of each substance. The primary endpoint was death, a cardiovascular event or end-stage renal disease. Survival analysis was performed using the Cox regression model. RESULTS: The patients' mean age was 62 ± 12 years, 97 were men, and 20 had diabetic nephropathy. The mean estimated glomerular filtration rate was 25.0 ± 12.1 mL/min per 1.73 m2 , which negatively correlated with MG but not with 3-DG and pentosidine. Forty-eight patients reached the primary endpoint. Compared with the lowest MG tertile, the hazard ratio for the primary endpoint was 7.57 (95% confidence interval (CI): 1.71-33.54) in the middle tertile and 27.00 (CI: 6.46-112.82) in the highest tertile. When adjusted for characteristics at baseline, the corresponding hazard ratio decreased to 2.09 (CI: 0.37-11.96) and 6.13 (CI: 0.97-38.82), but MG tertile remained an independent risk factor for the primary endpoint. However, 3-DG and pentosidine were not related to the primary outcome. CONCLUSION: Methylglyoxal has a close clinical association with CKD. Higher MG concentrations may contribute renal function deterioration in CKD. In CKD patients, MG concentration might be useful when determining the prognosis.

Liddle's-like syndrome associated with nephrotic syndrome secondary to membranous nephropathy: the first case report.

BACKGROUND: Liddle's syndrome is a rare monogenic form of hypertension caused by truncating or missense mutations in the C termini of the epithelial sodium channel (ENaC) ß or γ subunits. Patients with this syndrome present with early onset of hypertension, hypokalemia, metabolic alkalosis, hyporeninemia and hypoaldosteronism, and a potassium-sparing diuretics (triamterene or amiloride) can drastically improves the disease condition. Although elderly patients having these characteristics were considered to have Liddle's syndrome or Liddle's-like syndrome, no previous report has indicated that Liddle's-like syndrome could be caused by nephrotic syndrome of primary glomerular disease, which is characterized by urinary excretion of > 3 g of protein/day plus edema and hypoalbuminemia, or has explained how the activity function of ENaC could be affected in the setting of high proteinuria. CASE PRESENTATION: A 65-year-old Japanese man presented with nephrotic syndrome. He had no remarkable family history, but had a medical history of hypertension and hyperlipidemia. On admission, hypertension, spironolactone-resistant hypokalemia (2.43 mEq/l), hyporeninemic hypoaldosteronism, and metabolic alkalosis, which suggested Liddle's syndrome, were observed. Treatment with triamterene together with a steroid for nephrotic syndrome resulted in rapid and remarkable effective on improvements of hypertension, hypokalemia, and edema of the lower extremities. Renal biopsy revealed membranous nephropathy (MN) as the cause of nephrotic syndrome, and advanced gastric cancer was identified on screening examination for cancers that could be associated with the development of MN. After total gastrectomy, triamterene was not required and proteinuria decreased. A mutation in the ß or γ subunits of the ENaC gene was not identified. CONCLUSION: We reported for the first time a case of Liddle's-like syndrome associated with nephrotic syndrome secondary to MN. Aberrant activation of ENaC was suggested transient during the period of high proteinuria, and the activation was reversible with a decrease in proteinuria.

Distinct characteristics and outcomes in elderly-onset IgA vasculitis (Henoch-Schönlein purpura) with nephritis: Nationwide cohort study of data from the Japan Renal Biopsy Registry (J-RBR).

BACKGROUND: The clinical presentation and prognosis of adult and elderly patients with IgA vasculitis (Henoch-Schönlein purpura) accompanied by nephritis (IgAV-N) have not been investigated in detail. We therefore surveyed the features and outcomes of IgAV-N based on nationwide data derived from the Japan Renal Biopsy Registry (J-RBR). METHODS: This multi-center cohort study compared the clinicopathological parameters at diagnosis, initial therapies and outcomes between 106 adult (age 19-64 years) and 46 elderly (≥65 years) patients with IgAV-N who were registered in the J-RBR between 2007 and 2012. The primary end-points comprised a 50% increase in serum creatinine (sCr) values or end-stage kidney disease. Factors affecting a decrease in renal function were assessed using Cox proportional hazards models. RESULTS: Rates of hypertension, impaired renal function, hypoalbuminemia and crescentic glomerulonephritis were significantly higher among the elderly, than the adult patients. About 80% and 60% of the patients in both groups were respectively treated with corticosteroid and a renin-angiotensin system (RAS) blockade. Both groups had favorable renal survival rates for nine years (93.6% and 91.4% of the adult and elderly patients, respectively). Significantly more elderly than adult patients developed a 50% increase in sCr during a mean observation period of 3.9 years (21.7% vs. 4.7%, p = 0.012), and significantly fewer elderly, than adult patients achieved clinical remission (23.9% vs. 46.2%, p = 0.016). Multivariate analysis selected advanced age (≥65 years) and lower serum albumin values as independent prognostic factors for a decline in renal function, whereas steroid pulse therapy helped to preserve renal function. CONCLUSIONS: The renal prognosis of adult and elderly patients with IgAV-N was favorable when treated aggressively with corticosteroid and RAS blockade. However, the course of renal function should be carefully monitored in patients aged over 65 years and those with hypoalbuminemia.

Potential Benefit Associated With Delaying Initiation of Hemodialysis in a Japanese Cohort.

INTRODUCTION: Late referral to a nephrologist, the type of vascular access, nutritional status, and the estimated glomerular filtration rate (eGFR) at the start of hemodialysis (HD) have been reported as independent risk factors of survival for patients who begin HD. The aim of this study was to clarify the influence of the HD-free interval from the time of an eGFR of 10 ml/min per 1.73 m2 (IGFR10-HD) on patient outcome. METHODS: We enrolled 124 patients aged older than 20 years who had HD initiated in a general hospital. The predictive factor was the HD-free IGFR10-HD. The primary outcome was the relationship of the HD-free interval on death or the onset of a cardiovascular event. Survival analysis was performed using the Cox regression model. RESULTS: The median IGFR10-HD was 159 days (range: 2-1687 days). The median eGFR at the initiation of HD was 5.48 ml/min per 1.73 m2. Sixty-seven of 124 patients (54.0%) reached the primary outcome. Of these, 29 died and 38 experienced a cardiovascular event. In univariate analysis, older age, a history of cardiovascular disease, nephrologic care for <6 months, higher modified Charlson comorbidity index score, poor performance status, temporary catheter, edema, diabetic retinopathy, and nonuse of erythropoiesis-stimulating agent were statistically related to the primary outcome. The unadjusted hazard ratio per log-transformed IGFR10-HD was 0.393 (95% confidence interval [CI]; 0.244-0.635; P < 0.001) and the hazard ratio adjusted for confounding factors was 0.507 (95% CI: 0.267-0.956; P = 0.036). DISCUSSION: A longer HD-free IGFR10-HD was associated with a lower risk of death or a cardiovascular event. The interval could be considered an independent prognostic factor for outcomes in patients on HD.

Effects of cyclophosphamide on the prognosis of Japanese patients with renal vasculitis associated with anti-neutrophil cytoplasmic antibody-positive microscopic polyangiitis.

BACKGROUND: The aim of this study was to determine the efficacy of cyclophosphamide (CY) on anti-neutrophil cytoplasmic antibody (ANCA)-positive microscopic polyangiitis (MPA) with renal involvement in Japanese patients. METHODS: Eighty-two patients with newly diagnosed ANCA-positive MPA were enrolled in this retrospective study. Patients were divided into two groups based on whether they received combination therapy with a corticosteroid (CS) plus CY (CY group) or CS alone or with other therapies (non-CY group). The primary outcome was defined as the combination of death and end-stage renal disease (ESRD). RESULTS: The CY and non-CY groups included 29 and 53 patients, respectively. In the non-CY group, 31 patients were treated with CS alone, and 22 with a combination of CS and other therapeutics. The percentage of males and mean Birmingham vasculitis activity scores were higher in the CY group than those in the non-CY group, but other factors such as age, serum creatinine, serum albumin, or CRP at baseline were equivalent in the two groups. No differences were observed in remission rates using induction therapy for the two groups. However, the survival rate 5 years after induction therapy was lower in the CY group than in the non-CY group (0.50 vs. 0.73; P = 0.041), although the hazard ratio of CY for the primary outcome adjusted for all confounding factors was 1.321 [95 % confidence interval (CI), 0.662-2.637; P = 0.171]. CONCLUSIONS: CY may not have an additive effect on induction therapy with CS for Japanese patients with renal vasculitis associated with ANCA-positive MPA.

A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy.

BACKGROUND: The study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN). METHODS: Patients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria. RESULTS: During 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01-8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission. CONCLUSIONS: The results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified.

Gamma 1-heavy chain deposition disease accompanied by IgG kappa in serum, urine, and bone marrow.

A 32-year-old Japanese woman presented with hypertension, nephrotic syndrome, microhematuria, and severe hypocomplementemia. Her serum creatinine concentration increased from 1.46 mg/dL (129.0 µmol/L) to 3.46 mg/dL (305.8 µmol/L) over 1 month. Renal biopsy revealed Congo red-negative nodular glomerulosclerosis accompanied by mesangial proliferation. There was extensive staining of immunoglobulin (Ig) G in the glomerular and tubular basement membranes and expanded mesangial regions. Staining was negative for IgA, IgM, and kappa and lambda light chains and positive for the gamma 1 IgG subclass. Staining for constant domains of the gamma heavy chains showed a deletion of the first constant domain (CH1). Electron microscopy revealed electron-dense deposits in the glomerular and tubular basement membranes and mesangium. These findings indicated gamma 1-heavy chain deposition disease (HCDD). Serum and urine immunoelectrophoresis revealed an IgG kappa monoclonal band, whereas bone marrow biopsy revealed monoclonal plasmacytosis with positive staining for kappa chains. HCDD associated with kappa light chain is extremely rare. We report the first case of HCDD with IgG kappa detected in the serum, urine, and bone marrow.

Immunoglobulin A nephropathy with massive paramesangial deposits caused by anti-vascular endothelial growth factor therapy for metastatic rectal cancer: a case report and review of the literature.

BACKGROUND: Bevacizumab, a recombinant humanized monoclonal antibody for vascular endothelial growth factor, has been widely used in various cancers offering substantial clinical benefit. It is reportedly associated with development of high-grade proteinuria and nephrotic syndrome with the histology of thrombotic microangiopathy, but there has been no report describing the development of immunoglobulin A nephropathy in bevacizumab-treated patients. CASE PRESENTATION: A 68-year-old man with metastatic rectal cancer was treated with bevacizumab. He presented with hematuria and proteinuria 15 and 17 months, respectively, after bevacizumab initiation. Bevacizumab was stopped at 17 months. Renal biopsy at 19 months revealed immunoglobulin A nephropathy, with numerous paramesangial hemispherical deposits and thrombotic microangiopathy. Electron microscopy showed numerous paramesangial electron-dense deposits of various sizes, and subendothelial injuries. Proteinuria almost completely resolved 8 months after bevacizumab cessation, although hematuria persisted. Follow-up renal biopsy 11 months after bevacizumab cessation showed a marked decrease in mesangial immunoglobulin A deposits and paramesangial electron-dense deposits, which correlated with a gradual decrease in serum immunoglobulin A. CONCLUSION: This is the first case report that confirmed histologically the development and resolution of immunoglobulin A nephropathy during and after bevacizumab therapy. This case shows that there may be other mechanisms of glomerular injury by bevacizumab besides glomerular endothelial injury leading to thrombotic microangiopathy.

Long-term outcome and efficacy of cyclophosphamide therapy in Japanese patients with ANCA-associated microscopic polyangiitis: a retrospective study.

OBJECTIVE: The aim of this study was to elucidate the efficacy of cyclophosphamide (CY) in Japanese patients with antineutrophil cystoplasmic antibody (ANCA)-associated microscopic polyangiitis (MPA). METHODS: Sixty-four patients, newly diagnosed with ANCA-associated MPA were included in this retrospective study. The patients were divided into two groups based on whether they received combination therapy of CY and corticosteroid (CS) (CY group, n=29) or CS alone (CS group, n=35) for remission induction. The primary outcome was all-cause mortality. RESULTS: Most patients in the CY group were treated with oral CY. Between the two groups, there were no differences in the baseline characteristics except for a higher proportion of male patients in the CY group. The remission rate was not substantially different between the two groups (86.2% in the CY group vs. 91.4% in the CS group). The survival rate was slightly higher in the CY group than in the CS group (not statistically significant; 0.86 vs. 0.77 at 1 year and 0.73 vs. 0.64 at 5 years, p=0.648). In the CY group, the hazard ratio after adjusting for age, sex, Birmingham vasculitis activity score values, serum albumin levels and C-reactive protein (CRP) levels was 0.657 (95% CI, 0.254-1.699; p=0.386). CONCLUSION: We observed no increased efficacy of CY in ANCA-positive MPA in the Japanese patients, and hence, its efficacy may be limited in these patients.

Heavy chain deposition disease: an overview.

Heavy chain deposition disease (HCDD) is one of three entities of monoclonal immunoglobulin deposition disease, characterized histopathologically by the presence of nodular glomerulosclerosis and glomerular and tubular deposition of monoclonal heavy chains without associated light chains. Although HCDD is an extremely rare disease, >30 cases have been reported to date in the literature. Of these cases, only three cases have been reported in Japan. The majority of the patients presents with nephrotic syndrome, hematuria, and hypertension, and develop progressive renal failure with or without the complication of multiple myeloma. Some cases have been treated successfully using chemotherapy. Because of its rarity, a thorough understanding of HCDD is essential for both accurate diagnosis and adequate subsequent treatment.