Relapsing Tubulointerstitial Nephritis with Antimitochondrial M2 Antibody Accompanied by Pulmonary Involvement.

We herein report a 50-year-old woman who suffered from tubulointerstitial nephritis with antimitochondrial M2 antibody, distal renal tubular acidosis, and Fanconi syndrome. Our case also had interstitial pneumonia. After initially successful glucocorticoid therapy, tubulointerstitial nephritis and interstitial pneumonia relapsed. After the second successful round of glucocorticoid therapy, tubulointerstitial nephritis relapsed again and responded to glucocorticoid and azathioprine. This case might indicate (1) the association between pulmonary involvement and tubulointerstitial nephritis with antimitochondrial antibodies and (2) the need for a maintenance dose of glucocorticoid and immunosuppressants in tubulointerstitial nephritis with antimitochondrial antibodies.

Prediction of Acute Glomerular Filtration Rate Reductions Following Renin-angiotensin System Blockade in Chronic Kidney Disease: A Possible Application of Ultrasonography in Clinical Practice.

Objective Renal arteriolosclerosis is a risk factor for acute reductions in the glomerular filtration rate (GFR) when renin-angiotensin system (RAS) inhibitors are administered. Renal arteriolosclerosis can be detected by an increase in the resistive index (RI) on Doppler ultrasonography. The purpose of the present study is to determine whether or not the RI can predict acute GFR reductions following RAS blockade in chronic kidney disease (CKD). Methods We surveyed all CKD patients who were hospitalized in Otemae Hospital from January 2008 to December 2017. One hundred and eight patients who had been newly treated with RAS inhibitors were able to be followed for 14 weeks. The end point was an acute reduction in the GFR, defined as a decrease of ≥30%. Results Twenty-three of the 108 patients presented with acute GFR reductions. The cumulative probability of acute GFR reductions was 3.3% and 53% in patients with RI ≤0.70 and RI >0.70, respectively (p<0.001). A univariate Cox proportional-hazards analysis showed that the RI, age, GFR, systolic blood pressure, urinary protein excretion, diabetic kidney disease, coronary artery disease, and use of diuretics were significant variables. Multivariate hazard ratios were calculated from the RI and three established variables (age, GFR, diuretics), and the RI and use of diuretics were shown to be significant risk factors for acute GFR reductions. Conclusion These results suggest that an increase in the RI, as well as the use of diuretics, may be risk factors for acute GFR reductions following RAS blockade.

Chronological renal resistive index increases related to atherosclerotic factors, and effect of renin-angiotensin system inhibitors.

BACKGROUND: Renal resistive index (RI) calculated using renal Doppler ultrasonography (RDU) has recently been considered a clinically important indicator of renal outcome, survival, and systemic arteriosclerotic disorders. However, the cause of RI elevation remains unclear. The present study was an effort to first, identify the factors related to RI elevation, and second, understand the effect of renin-angiotensin system inhibitors (RAS-Is) on renal RI elevation. METHODS: We carried out this single-center case-control study among 100 CKD patients, recruited from outpatients who underwent RDU more than twice, at least a year apart. The rate of renal RI change per year (dRIpy) was chosen as the dependent variable: [(last examined renal RI-initial examined renal RI)/(initial examined renal RI × period of observation) × 100 (%/year)]. We examined the association between dRIpy and other clinical and biological data. RESULTS: Among 100 CKD patients, the average serum creatinine and eGFR were 1.76 ± 0.84 mg/dL and 37.0 ± 18.2 ml/min/1.73 m2, respectively. The average dRIpy in all patients was 1.8 ± 1.4%/year. The linear multiple regression demonstrated that dRIpy was positively associated with the presence of diabetes mellitus (DM) and high low-density lipoprotein cholesterol (LDL) levels, and negatively with eGFR and RAS-I use. CONCLUSIONS: This study demonstrated that the elevation of RI was related to DM, eGFR, high LDL, and the use of RAS-Is. In particular, RAS-Is could contribute towards suppressing the elevation of RI in CKD patients and towards preventing the development of renal failure in CKD patients.

Nephrotic Syndrome with Thrombocytopenia, Lymphadenopathy, Systemic Inflammation, and Splenomegaly.

Nephrotic syndrome can be caused by various diseases, from primary kidney diseases to systemic diseases. A kidney biopsy is useful for confirming the causes of nephrotic syndrome and in its management. We herein describe a case of nephrotic syndrome with thrombocytopenia, lymphadenopathy, systemic inflammation, splenomegaly, kidney enlargement, and progressive renal insufficiency. A kidney biopsy showed endothelial swelling with mild interstitial fibrosis and tubular atrophy. This case met the diagnostic criteria for TAFRO syndrome. Little is known about TAFRO syndrome, especially in relation to the associated kidney pathophysiology. The accumulation of a greater number of cases in which the kidney biopsy findings are investigated is needed to clarify the pathogenesis of kidney involvement in this condition.

Renal dysfunction can be a common complication in patients with myotonic dystrophy 1.

Although renal failure can be a life-threatening complication even in neuromuscular disorders (NMDs), renal dysfunction is easily overlooked because muscle atrophy decreases the serum creatinine level. Renal function was retrospectively assessed using cystatin C (CysC) in various NMDs to clarify the differences among diseases. As is in the general population, age was correlated to CysC, and female patients showed lower CysC levels. Although elevated CysC was frequent in myotonic dystrophy 1 (DM1: MIM 160900) and motor neuron disorders, an inter-disease comparison by sex adjusted for age showed that only DM1 had a higher CysC compared to other diseases. Multivariate linear regression with the stepwise method also suggested that the number of CTG repeats had an impact on CysC levels. In two autopsy DM1 cases, nephrosclerotic changes were observed even though they were in their forties. These facts suggested a disease-specific pathomechanism for renal dysfunction in DM1. Although further study is required, renal function should be carefully monitored in patients with DM1.

Distinct α-intercalated cell morphology and its modification by acidosis define regions of the collecting duct.

During metabolic acidosis, the cortical collecting duct (CCD) of the rabbit reverses the polarity of bicarbonate flux from net secretion to net absorption, and this is accomplished by increasing the proton secretory rate by α-intercalated cells (ICs) and decreasing bicarbonate secretion by ß-ICs. To better characterize dynamic changes in H(+)-secreting α-ICs, we examined their morphology in collecting ducts microdissected from kidneys of normal, acidotic, and recovering rabbits. α-ICs in defined axial regions varied in number and basolateral anion exchanger (AE)1 morphology, which likely reflects their relative activity and function along the collecting duct. Upon transition from CCD to outer medullary collecting duct from the outer stripe to the inner stripe, the number of α-ICs increases from 11.0 ± 1.2 to 15.4 ± 1.11 and to 32.0 ± 1.3 cells/200 µm, respectively. In the CCD, the basolateral structure defined by AE1 typically exhibited a pyramidal or conical shape, whereas in the medulla the morphology was elongated and shallow, resulting in a more rectangular shape. Furthermore, acidosis reversibly induced α-ICs in the CCD to acquire a more rectangular morphology concomitant with a transition from diffusely cytoplasmic to increased basolateral surface distribution of AE1 and apical polarization of B1-V-ATPase. The latter results are consistent with the supposition that morphological adaptation from the pyramidal to rectangular shape reflects a transition toward a more "active" configuration. In addition, α-ICs in the outer medullary collecting duct from the outer stripe exhibited cellular morphology strikingly similar to dendritic cells that may reflect a newly defined ancillary function in immune defense of the kidney.

Insights into acidosis-induced regulation of SLC26A4 (pendrin) and SLC4A9 (AE4) transporters using three-dimensional morphometric analysis of ß-intercalated cells.

The purpose of this study was to examine the three-dimensional (3-D) expression and distribution of anion transporters pendrin (SLC26A4) and anion exchanger (AE)4 (SLC4A9) in ß-intercalated cells (ß-ICs) of the rabbit cortical collecting duct (CCD) to better characterize the adaptation to acid-base disturbances. Confocal analysis and 3-D reconstruction of ß-ICs, using identifiers of the nucleus and zona occludens, permitted the specific orientation of cells from normal, acidotic, and recovering rabbits, so that adaptive changes could be quantified and compared. The pendrin cap likely mediates apical Cl(-)/HCO3 (-) exchange, but it was also found beneath the zona occludens and in early endosomes, some of which may recycle back to the apical membrane via Rab11a(+) vesicles. Acidosis reduced the size of the pendrin cap, observed as a large decrease in cap volume above and below the zona occludens, and the volume of the Rab11a(+) apical recycling compartment. Correction of the acidosis over 12-18 h reversed these changes. Consistent with its proposed function in the basolateral exit of Na(+) via Na(+)-HCO3 (-) cotransport, AE4 was expressed as a barrel-like structure in the lateral membrane of ß-ICs. Acidosis reduced AE4 expression in ß-ICs, but this was rapidly reversed during the recovery from acidosis. The coordinate regulation of pendrin and AE4 during acidosis and recovery is likely to affect the magnitude of acid-base and possibly Na(+) transport across the CCD. In conclusion, acidosis induces a downregulation of AE expression in ß-ICs and a diminished presence of pendrin in apical recycling endosomes.

[Case of microscopic polyangiitis accompanied by central nervous system symptoms and brain vasculitis observed histopathologically].

A 65-year-old-man complained of coughing and fever. The urine showed microscopic hematuria. The level of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) was 167 EU. Two months later, he was admitted to our hospital with pulmonary hemorrhage and progressive renal dysfunction. He was treated with intravenous methylprednisolone followed by oral prednisolone with plasma exchanges, and his first pulmonary hemorrhage was relieved. Three weeks later, he suffered from a second diffuse pulmonary hemorrhage with central nervous system symptoms. He was treated again with intravenous methylprednisolone, plasma exchanges, and also intravenous pulse cyclophosphamide (IVCY), but he died of respiratory failure. Autopsy findings revealed microscopic polyangiitis (MPA)in the brain as well as in the lung, kidney and gastrointestinal system. The histopathological findings suggested that cerebral nervous system symptoms could have been caused by brain vasculitis in this case.

Influence of proteinuria on renal Doppler sonographic measurements in chronic kidney disease and in diabetes mellitus.

PURPOSE: To evaluate the influence of proteinuria on renal Doppler sonographic (US) measurements in patients with chronic kidney disease (CKD) with or without diabetes mellitus (DM). METHODS: Renal resistance index (RI), pulsatility index (PI), and maximum kidney length were measured by US in 113 patients suffering from CKD without DM (non-DM CKD patients) and in 120 patients with diabetic nephropathy (DM patients). Other data collected were sex, age, body mass index, blood pressure, estimated glomerular filtration rate, urinary protein level, and medical history. The effect of proteinuria on RI and PI was evaluated using single regression analyses, multiple regression analyses, and comparison of regression lines. RESULTS: Single and multiple regression analyses revealed that RI and PI in the two subgroups and in the entire group of patients were correlated with urinary protein level (p < 0.05). Comparison of regression lines of each subgroup showed statistically significant differences in two regression intercepts concerning these indices in relation to urinary protein level (p < 0.001, RI: 0.71 in non-DM CKD patients versus 0.76 in DM patients, PI: 1.39 in non-DM CKD patients versus 1.60 in DM patients) (p < 0.001). CONCLUSIONS: Renal RI and PI can reflect damages related to proteinuria and DM.

Adaptation to metabolic acidosis and its recovery are associated with changes in anion exchanger distribution and expression in the cortical collecting duct.

It is well known that acid/base disturbances modulate proton/bicarbonate transport in the cortical collecting duct. To study the adaptation further we measured the effect of three days of acidosis followed by the rapid recovery from this acidosis on the number and type of intercalated cells in the rabbit cortical collecting duct. Immunofluorescence was used to determine the expression of apical pendrin in ß-intercalated cells and the basolateral anion exchanger (AE1) in α-intercalated cells. Acidosis resulted in decreased bicarbonate and increased proton secretion, which correlated with reduced pendrin expression and the number of pendrin-positive cells, as well as decreased pendrin mRNA and protein abundance in this nephron segment. There was a concomitant increase of basolateral AE1 and α-cell number. Intercalated cell proliferation did not seem to play a role in the adaptation to acidosis. Alkali loading for 6-20 h after acidosis doubled the bicarbonate secretory flux and reduced proton secretion. Pendrin and AE1 expression patterns returned to control levels, demonstrating that adaptive changes by intercalated cells are rapidly reversible. Thus, regulation of intercalated cell anion exchanger expression and distribution plays a key role in adaptation of the cortical collecting duct to perturbations of acid/base.

Vesiculobullous dermatomyositis with panniculitis without muscle disease.

Vesicles and bullae formation is rare in dermatomyositis. We describe a 60-year-old woman who presented with vesiculobullous dermatomyositis with panniculitis and no muscle disease.