Genetic Diagnosis of Adult Hemodialysis Patients With Unknown Etiology.

Introduction: Kidney disease of unknown etiology accounts for 1 in 10 adult end-stage renal disease (ESRD) cases worldwide. The aim of this study is to clarify the genetic background of patients with chronic kidney disease (CKD) of unknown etiology who initiated renal replacement therapy (RRT) in adulthood. Methods: This is a multicenter cross-sectional cohort study. Of the 1164 patients who attended 4 dialysis clinics in Japan, we first selected patients who started RRT between the ages of 20 and 49 years. After excluding patients with apparent causes of CKD (e.g., diabetic nephropathy, polycystic kidney disease (PKD) with family history, patients who underwent renal biopsy), 90 patients with CKD of unknown cause were included. The 298 genes associated with CKD were analyzed using capture-based targeted next-generation sequencing. Results: Of the 90 patients, 10 (11.1%) had pathogenic variants in CKD-causing genes and 17 (18.9%) had variant of unknown significance (VUS). Three patients had PKD1 pathogenic variants, and 1 patient had PKD1 and COL4A4 pathogenic variants. In addition, 2 patients were diagnosed with atypical hemolytic uremic syndrome (aHUS) due to C3 or CFHR5. One patient each was diagnosed with Alport syndrome due to COL4A4 and COL4A3 variants, nephronophthisis due to NPHP1 variants, Fabry disease due to GLA variants, and autosomal-dominant tubulointerstitial kidney disease due to UMOD variants. Genetic diagnoses were not concordant with clinical diagnoses, except for patients with PKD1 variant. Conclusion: This largest study on genetic analysis in hemodialysis-dependent adults revealed the presence of undiagnosed inherited kidney diseases.

Expression levels and DNA methylation profiles of the growth gene SHOX in cartilage tissues and chondrocytes.

All attempts to identify male-specific growth genes in humans have failed. This study aimed to clarify why men are taller than women. Microarray-based transcriptome analysis of the cartilage tissues of four adults and chondrocytes of 12 children showed that the median expression levels of SHOX, a growth gene in the pseudoautosomal region (PAR), were higher in male samples than in female samples. Male-dominant SHOX expression was confirmed by quantitative RT-PCR for 36 cartilage samples. Reduced representation bisulfite sequencing of four cartilage samples revealed sex-biased DNA methylation in the SHOX-flanking regions, and pyrosequencing of 22 cartilage samples confirmed male-dominant DNA methylation at the CpG sites in the SHOX upstream region and exon 6a. DNA methylation indexes of these regions were positively correlated with SHOX expression levels. These results, together with prior findings that PAR genes often exhibit male-dominant expression, imply that the relatively low SHOX expression in female cartilage tissues reflects the partial spread of X chromosome inactivation into PAR. Altogether, this study provides the first indication that sex differences in height are ascribed, at least in part, to the sex-dependent epigenetic regulation of SHOX. Our findings deserve further validation.

Postoperative deviation in Wassel types II and III radial polydactyly: a retrospective analysis of 73 thumbs.

This study examined the relationship between osteochondral stability and postoperative deviation at the interphalangeal (IP) joint in Wassel types II and III radial polydactyly. Cases with cartilaginous fusion between the radial distal phalanx and the proximal phalanx were classified as type IIB, while the remaining cases were categorized as type IIA. In conventional surgery, the cartilage was routinely resected on the radial aspect of the proximal phalangeal head, while in the modified procedure, this was preserved to avoid postoperative radial deviation. Postoperatively, there was no significant difference between both procedures in type IIA thumbs regarding IP joint deviation, whereas in type IIB/III thumbs, IP joint deviation was significantly higher in the conventional group (mean 19° [SD 16°]) compared to the modified group (mean 0.8° [SD 4.9°]). Surgeons should exercise caution against excessive cartilage excision to preserve osteochondral stability during procedures, especially for type IIB and III radial polydactylies.Level of evidence: IV.

A Prospective Randomized Comparison of Variable-Angle and Fixed-Angle Volar Locking Plating for Intra-Articular Distal Radius Fractures.

PURPOSE: To compare clinical and radiographic outcomes of using a variable-angle volar locking plate (VAVLP) with those of using a fixed-angle volar locking plate (FAVLP) for treating unstable intra-articular fractures of the distal radius. METHODS: One hundred twenty patients with unstable intra-articular fractures of the distal radius were randomized to open reduction and internal fixation with a VAVLP (n = 60) or an FAVLP (n = 60). Supplementary methods (eg., Kirschner wire fixation) were required in 4 patients with a VAVLP and 9 with an FAVLP. Clinical outcomes were evaluated at 6 weeks, 3 months, 6 months, and 1 year after surgery. Posteroanterior and lateral radiographs were used to measure standard radiographic parameters before surgery, in the immediate postoperative period, and at 1 year. Plate prominence and articular congruity were quantified using computed tomography at 6 months. RESULTS: There were no significant differences in any clinical outcome between the groups at any follow-up time. Volar tilt was significantly greater in patients treated with a FAVLP in the immediate postoperative period (8° vs 6°) and at 1 year (8° vs 5°). Although significant differences were not found in articular gap or stepoff between the 2 plates, the distal and volar prominence of the VAVLP was significantly greater than that of the FAVLP at 6 months. Significantly more patients treated with a VAVLP had a complication (38% vs 19%). However, most secondary surgeries were performed for hardware removal, and no patients from either group had complex regional pain syndrome or tendon rupture. CONCLUSIONS: Patients with intra-articular distal radius fractures can expect good functional and radiographic outcomes with VAVLP or FAVLP fixation. The VAVLP may be more prone to technical errors, leading to complications, whereas the FAVLP is more likely to require supplementary fixation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

Normal values and ranges of the lateral capitello-humeral angle in healthy children.

The lateral capitello-humeral angle (LCHA), which is an index of sagittal alignment of the elbow, has gradually been adopted for the postoperative assessment of radiographic results. However, the normal values and ranges of the LCHA remain unclear. A retrospective cohort study was performed to evaluate the normal values and ranges of the LCHA in a sample of healthy children with even distributions of age, sex and laterality. A total of 168 radiographs of the elbows of healthy children (age range, 0-11 years) with even distributions of age, sex and laterality were reviewed. The primary aim was to analyze the normal values and ranges of the LCHA categorized by age, sex and laterality. The secondary aim was to assess the association of the LCHA with increasing age. The LCHA between sex or laterality in each age category was also compared. The mean LCHA of the 168 patients was 47.1° (range, 27°-63°). There was a weak association between the LCHA and increasing age (r = 0.41). The mean LCHA in females (49.1°) was significantly larger than that in males (45.1°). Significant sex-related differences were observed in age categories between 2 and 7 years. Results of this study will be useful in the postoperative radiographic assessment of sagittal alignment of the elbow in children.

Motion of the distal radioulnar joint in extension and flexion of the wrist using axial CT imaging of healthy volunteers.

BACKGROUND: The midcarpal joint and the radiocarpal joint contribute to the extension and flexion of the wrist. Little is known about the contribution of the distal radioulnar joint (DRUJ) to the extension and flexion of the wrist. This study evaluated the ulnar motion in extension and flexion of the wrist using computed tomography (CT) imaging. METHODS: A total of 30 wrists of healthy volunteers were enrolled. CT images of the axial sections of the DRUJ were obtained with 3 different positions of the wrist: 0° of extension (straight position), maximum active extension, and maximum active flexion. Each wrist motion was performed with 3 different forearm positions: neutral, pronation, and supination. Ulnar position at the DRUJ level was measured and ulnar position with the wrist in straight position was defined as baseline. The ulnar position was recorded as positive value when the position of the ulnar head was volar side and negative value when the position of the ulnar head was dorsal side. The difference from baseline in a position of maximum extension and flexion was evaluated. RESULTS: In forearm neutral position and pronation, a value of ulnar position in maximum wrist flexion is significantly negative compared to that in the wrist straight position: the ulnar head moved dorsally from the wrist straight position to wrist flexion. In forearm supination, a value of ulnar position in maximum wrist extension is significantly positive compared to that in the wrist straight position: the ulnar head moved to the volar side from the wrist straight position to wrist extension. CONCLUSIONS: The ulnar head moves during extension and flexion of the wrist. The direction of the ulnar motion was different according to the wrist and forearm position.

Three-dimensional preoperative planning for adult acute plastic bowing of the ulna.

CASE: We report a case of adult acute plastic deformity of the ulna. Ulnar osteotomy was planned using 3-dimensional (3D) surface data from both injured and intact sides using surface registration technique. Opening wedge osteotomy was planned to correct the position of the ulnar fovea with respect to the proximal ulna. The position of the plate and direction of the screws were decided preoperatively. The operation was performed with reference to a 3D-printed, reduced model. The preoperatively limited pronation and supination of the patient were significantly improved as of 2 years postoperatively. Our preoperative method has several advantages. The risk of nonunion is low because the hinge-side bone cortex remains intact. The surgical procedure is simple, because plate position and direction of drilling are both decided preoperatively. In addition, correction of alignment can be achieved gradually by inserting screws through the plate and checking the range of motion of the forearm. CONCLUSION: Our 3D preoperative simulation aimed to correct the rotational axis of the forearm. The surgical procedure was greatly facilitated using the 3D-printed, reduced model for reference.

Normal value and range of the humerus-elbow-wrist angle in a sample of healthy children with even distributions of age, sex, and laterality.

This study was performed to evaluate the normal value of the humerus-elbow-wrist angle (HEWA) in a sample of healthy children with even distributions of age, sex, and laterality. A total of 168 radiographs of the elbows of healthy children with even distributions of age, sex, and laterality were reviewed. The mean HEWA was 12.1° (range: 5°-20°). The value of HEWA was significantly associated with increasing age. Neither sex nor side showed significant differences for the HEWA. The data should be useful for postoperative radiographic assessment of cubitus varus or valgus deformities.

The relationship between the morphological axis and the kinematic axis of the proximal radius.

PURPOSE: Surgical procedures for impaired forearm rotation such as for chronic radial head dislocation remain controversial. We hypothesized that the morphological axis of the proximal radius is important for stable forearm rotation, and we aimed to clarify the relationship between the morphological axis and the kinematic axis of the proximal radius using four-dimensional computed tomography (4DCT). METHODS: Ten healthy volunteers were enrolled. Four-dimensional CT of the dominant forearm during supination and pronation was obtained. The rotation axis of forearm rotation was calculated from all frames during supination and pronation. The principle axis of inertia, which represents the most stable rotation axis of a rigid body, was calculated for the proximal radius by extending its surface data incrementally by 1% from the proximal end. The angle between the kinematic rotation axis and the morphological rotation axis of each length was calculated. RESULTS: The rotation axis of the forearm was positioned on the radial head 0.0 mm radial and 0.4 mm posterior to the center of the radial head proximally and 2.0 mm radial and 1.2 mm volar to the fovea of the ulnar head distally. The principle axis at 15.9% of the length of the proximal radius coincided with the forearm rotation axis (kinematic axis). Individual differences were very small (SD 1.4%). CONCLUSION: Forearm rotation was based on the axis at 16% of the length of the proximal radius. This portion should be aligned in cases of severe morphological deformity of the radial head that cause "rattling motion" of the radial head after reduction procedures.

A Novel Surgical Technique for Chronic Mallet Finger Injury: A Case Report.

A 39-year-old man injured his left little finger and was diagnosed with chronic tendon mallet with -50° of extension and 80° of flexion at the DIP joint. We performed an anatomical reconstruction of the terminal tendon and both lateral bands with divided palmaris longus tendon grafting. Postoperative range of motion at the DIP joint improved to -5° of extension with no flexion loss. We demonstrated a novel surgical technique for chronic tendon mallet injury that might represent a useful choice for the treatment of chronic mallet finger injury.

Acute Compartment Syndrome in the Forearm with Trans-Ulnar Single Incision.

We report a case of ulnar nerve palsy caused by diaphyseal fractures of the forearm and acute compartment syndrome. Trans-ulnar single incision with a fasciotomy of the volar and dorsal compartments was used to fix the ulna. Full recovery of the ulnar nerve was achieved six months after the surgery. In cases of acute compartment syndrome with ulnar fracture, a trans-ulnar incision with compartment release is effective for the fixation of the ulna.

IgA-dominant postinfectious glomerulonephritis associated with Escherichia coli infection caused by cholangitis.

A 76-year-old man with a history of type 2 diabetes mellitus was admitted with cholangitis caused by cholangiocarcinoma. Cholangitis with Escherichia coli (E. coli) bacteremia recurred due to the unstable bile drainage. At 1 month after recurrence, rapidly progressive glomerulonephritis with nephrotic syndrome was manifested. Renal biopsy findings were consistent with immunoglobulin A (IgA)-dominant postinfectious glomerulonephritis (PIGN). After ensuring that the recurrent cholangitis was controlled by drainage and antibiotic therapy, oral prednisolone was initiated, and the patient's renal function and proteinuria subsequently gradually improved. This is the first case report of IgA-dominant PIGN associated with cholangitis caused by E. coli infection.

Nephrotic-range proteinuria and interstitial nephritis associated with the use of a topical loxoprofen patch.

A 76-year-old woman with a history of lumbar fracture and marked proteinuria, bilateral pitting edema, malaise and pruritus was referred for an evaluation of an impaired renal function. A renal biopsy led to a tentative diagnosis of acute interstitial nephritis (AIN) with minimal change disease caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Following the discontinuation of oral NSAIDs, the patient's symptoms disappeared spontaneously. However, nephrotic-range proteinuria relapsed one month after discharge, following loxoprofen patch use. The withdrawal of the topical loxoprofen patches once again resulted in the disappearance of all symptoms. This is the first case report of nephrotic-range proteinuria and AIN secondary to topical NSAID patch use.

Decreased mobility after starting dialysis is an independent risk factor for short-term mortality after initiation of dialysis.

AIM: Impaired mobility at the onset of dialysis is considered one of the most important risk factors for short-term mortality after initiation of dialysis in elderly patients. However, whether a decline in mobility after starting dialysis also affects mortality is unclear. METHODS: A total of 202 patients (age, >75 years; mean, 80.4 ± 4.3) were enrolled in this retrospective cohort study in Yokosuka, Japan. They were divided into three subgroups by mobility: independent mobility at onset of dialysis and preservation of mobility after starting dialysis (group 1, n = 104); independent mobility at onset of dialysis and decline in mobility after starting dialysis (group 2, n = 48); and impaired mobility at onset of dialysis (group 3, n = 50). They were followed for 6 months after starting dialysis. A Cox proportional hazards model was used to evaluate the association between mobility and mortality. RESULTS: A total of 24.8% of patients had impaired mobility at the start of dialysis, and 68.9% declined in mobility after starting dialysis. In multivariate Cox proportional hazards analysis, the adjusted hazard ratios of groups 2 and 3 compared with group 1 were 3.80 (95% confidence interval, 1.02-14.10) and 4.94 (95% confidence interval, 1.42-17.10), respectively. CONCLUSION: Not only impaired mobility at the start of dialysis but also a decline in mobility after starting dialysis is associated with short-term mortality after initiation of dialysis.

Periodic hypokalemia associated with cyclic Cushing's syndrome.

A 69-year-old woman presented with periodic hypertension, edema, and hypokalemia that occurred within an interval of a few weeks. Her laboratory test values showed autonomously elevated plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations. The patient's Cushingoid features were not evident on first admission. Several weeks later, in spite of constant oral potassium supplementation, severe hypokalemia recurred with Cushingoid features and worsening symptoms of leg edema and pigmentation, which spontaneously disappeared within a few days. Her periodic symptoms occurred in parallel with fluctuations of plasma ACTH and cortisol concentrations. A series of endocrinological and pituitary imaging findings led to a tentative diagnosis of cyclic Cushing's syndrome caused by ectopic ACTH secretion. However, chest and abdominal computed tomography did not reveal any candidate lesion. The patient's periodic hypercortisolemia and symptoms were well controlled after treatment with metyrapone plus dexamethasone. This is a very rare case of periodic hypokalemia and hypertension caused by cyclic Cushing's syndrome.

Sarcoidosis in a chronic dialysis patient diagnosed by sarcoidosis-related hypercalcemia with no common systemic clinical manifestations: a case report and review of the literature.

Sarcoidosis is a systemic granulomatous disease of unknown origin. We herein report a case of sarcoidosis in a chronic dialysis patient diagnosed by hypercalcemia without any common clinical manifestations. The onset of sarcoidosis in chronic dialysis patients is rare; to the best of our knowledge, only 23 cases have been reported. Evaluation of the 23 previously published cases revealed that a diagnosis of sarcoidosis was often achieved by the presence of sarcoidosis-related hypercalcemia without any common clinical presentations, as in the present case. This characteristic may arise from a specific immune deficiency and the unique physiology of 1,25-dihydroxyvitamin D3, a main cause of sarcoidosis-related hypercalcemia, in chronic dialysis patients. These clinical features may be useful to understand the pathogenesis of sarcoidosis.

Post-staphylococcal infection Henoch-Schönlein purpura nephritis: a case report and review of the literature.

A 37-year-old man developed Henoch--Schönlein purpura nephritis (HSPN) with nephrotic syndrome and rapidly progressive glomerulonephritis after otitis media and externa due to methicillin-resistant Staphylococcus aureus infection. Despite resolution of the infection and prednisolone therapy, his kidney disease worsened. However, the addition of cyclosporine A finally resulted in complete remission of the nephrotic syndrome. A review of similar cases with post-Staphylococcal infection HSPN revealed strong similarities between this entity and immunoglobulin A-dominant postinfectious glomerulonephritis (IgA-PIGN), an increasingly recognized form of PIGN typically associated with Staphylococcal infection, in both clinical and morphological features. Post-Staphylococcal infection HSPN may constitute a subgroup of IgA-PIGN.

Anti-centromere antibody is an independent risk factor for chronic kidney disease in patients with primary biliary cirrhosis.

BACKGROUND: Anti-centromere antibody (ACA), a typical autoantibody of systemic sclerosis, is also detected in primary biliary cirrhosis (PBC). However, its pathogenic role is not fully understood. The aim of this study was to determine the association between ACA and kidney function in PBC. METHODS: A cohort of 37 patients diagnosed as having PBC from July 2001 to November 2011 at Yokosuka Kyosai Hospital was retrospectively analyzed for a follow-up period of 12 months. The annual rate of estimated glomerular filtration rate (eGFR) decline within 1 year after the diagnosis was evaluated. The factors associated with eGFR decline were evaluated by linear regression analysis and logistic regression analysis. RESULTS: Overall, 37 PBC patients were included, of whom 12 (32%) had ACA. The patients with ACA had a lower eGFR (65.9 ± 19.9 vs. 80.3 ± 12.1 mL/min/1.73 m(2), P = 0.01), a higher likelihood of chronic kidney disease (CKD) (58 vs. 4%, P = 0.0005), and a higher rate of annual eGFR decline (-4.3 ± 5.1 vs. 0.2 ± 4.6 mL/min/year, P = 0.01) than those without ACA. Univariate regression analysis and multivariate regression analysis adjusted for potential cofounders including age, eGFR, sex, diabetes mellitus, and hypertension showed that ACA was associated with eGFR decline (P = 0.011 and 0.017, respectively). Multivariate logistic regression analysis adjusted for these cofounders showed that ACA was associated with eGFR decline less than -4 mL/min/year (odds ratio 7.21, 95% confidence interval 0.93-56.1, P = 0.059). CONCLUSIONS: ACA is an independent risk factor for CKD in PBC. Evaluation of ACA and kidney function is necessary to prevent CKD progression in PBC patients.