Spontaneous Remission of Minimal Change Disease in a Colon Cancer Patient: A Case Report.

Introduction: Minimal change disease (MCD) is most often primary but may occur secondary to other systemic diseases such as malignancy. In secondary MCD, spontaneous remission of nephrotic syndrome after the treatment of related diseases without steroid therapy is rare. Case Presentation: A 78-year-old man visited the outpatient clinic with foamy urine and generalized edema that had persisted for 2 months. The patient had nephrotic syndrome. Before a kidney biopsy, he underwent several tests to determine the secondary cause of the nephrotic syndrome. The serum CEA was slightly elevated, and colon cancer was detected in the sigmoid colon. MCD was diagnosed from a kidney biopsy. He immediately underwent surgery for colon cancer. Complete remission of the MCD was achieved within 2 weeks after surgery. Conclusion: Here, we report a rare case of a patient with secondary MCD who successfully achieved spontaneous remission after colon cancer surgery.

IgA nephropathy with minimal change disease associated with primary Sjögren's syndrome: A case report.

RATIONALE: Only 1 case of IgA nephropathy (IgAN) with minimal change disease (MCD) associated with primary Sjögren's syndrome (SS) has been reported. We additionally describe IgAN with MCD associated with primary SS. PATIENT CONCERNS: A 80-year-old woman visited our hospital complaining of generalized edema that had started 4 weeks prior. She reported a sense of thirst and dry eye for the last 5 years. DIAGNOSES: Her initial laboratory findings were compatible with nephrotic syndrome; both the antinuclear antibody (1:80) and anti-SS-A (Ro) antibody (200 U/mL) tests were positive. A salivary gland scan revealed markedly decreased uptake for both the parotid and submandibular glands. The Schirmer test was positive. The random urine protein/creatinine ratio was 10 mg/mg. Renal biopsy was compatible with IgAN with superimposed MCD. INTERVENTIONS: Furosemide was intravenously administered with intermittent albumin infusion for her edema control. She was started on prednisone 40mg daily for 6 weeks, which was tapered to 5 mg for another 6 months after starting prednisolone. OUTCOMES: Over the next 6 months, her edema improved and the proteinuria decreased significantly. LESSONS: Physician should suspect IgA with MCD when patient with SS clinically showed nephrotic syndrome, and perform renal biopsy for pathologically diagnosis and appropriate treatment.

Special Issue: Resistance to Targeted Therapies in Human Cancer.

Cancer is the second leading cause of death worldwide, accounting for approximately 10 million deaths in 2020 [...].

ECM1 is associated with endocrine resistance in ER+ breast cancers.

Extracellular matrix protein 1 (ECM1) is associated with a poor prognosis of breast cancers. However, the role of ECM1 with endocrine resistance in estrogen receptor-positive (ER+) breast cancers has not been elucidated yet. We show that ECM1 promotes endocrine resistance in ER+ breast cancers. ECM1 is overexpressed in luminal breast cancer patients compared to the basal type of breast cancer. Significantly, higher expression of ECM1 is associated with poor response to endocrine therapies in luminal B breast cancer patients. We found that ECM1 is upregulated in CAMA1 and MDA-MB-361 cells grown in long-term estrogen-deprived (LTED) conditions. Moreover, the ablation of ECM1 significantly inhibited the proliferation of CAMA1 LTED and MDA-MB-361 LTED cells. Finally, an interrogation of a dataset containing transcriptome and proteome of breast cancer cell lines revealed that the level of ECM1 mRNA is positively correlated with that of phosphorylated Src. Based on these findings, we strongly suggest that ECM1 significantly contributes to the acquisition of endocrine resistance in ER+ breast cancers by the activation of Src.

Acute kidney injury due to direct infiltration by lymphoplasmacytic lymphoma secreting IgG paraproteins: A case report.

INTRODUCTION: Waldenström's macroglobulinemia is a lymphoplasmacytic lymphoma (LPL) associated with a monoclonal immunoglobulin M protein. Although acute kidney injury (AKI) due to immunoglobulin M paraprotein infiltration into the renal interstitium has been reported, there has been no report of AKI with invasion of the immunoglobulin G paraprotein into the renal interstitium in a patient with LPL. PATIENT CONCERNS: A 65-year-old male was admitted to our hospital with fatigue and decreased renal function. He complained of a 3-kg weight loss in the last 3 months. DIAGNOSIS: The initial blood urea nitrogen and serum creatinine levels were 55.9 and 1.83 mg/dL, respectively. Serum protein electrophoresis revealed a monoclonal component (3.5 g/dL) in the gamma region and immunofixation electrophoresis showed an immunoglobulin G kappa monoclonal protein. Renal pathology revealed that CD3-CD20+ CD138+ lymphoid cells had infiltrated the renal interstitium. A bone marrow biopsy was compatible with LPL. INTERVENTIONS: Intravenous methylprednisolone (1 mg/kg) was administered after confirming the renal pathological findings. OUTCOMES: Serum creatinine decreased to 0.8 mg/dL 14 days after treatment. CONCLUSIONS: Physicians should recognize LPL secreting various immunoglobulins as a possible cause of AKI when renal failure of unknown etiology and serum immunoglobulin paraprotein is present. A kidney biopsy should be performed for definitive diagnosis and appropriate management.

Acute interstitial nephritis associated with ingesting a Momordica charantia extract: A case report.

RATIONALE: Momordica charantia is often used to treat type 2 diabetes mellitus in Korea. Drug-induced acute interstitial nephritis (AIN) accounts for 60% to 70% of AIN cases. However, only 1 case of AIN associated with ingesting M charantia has been reported in the English literature. We report an extremely rare case of AIN that occurred after a patient ingested a pure M charantia extract over 7 months. PATIENT CONCERNS: A 60-year-old Korean woman was admitted to our hospital for a renal biopsy. Her renal function had decreased gradually over the last 9 months without symptoms or signs. DIAGNOSIS: Her blood urea nitrogen and serum creatinine levels were 29.7 mg/dL (range: 8.0-20.0 mg/dL) and 1.45 mg/dL (range: 0.51-0.95 mg/dL) on admission. Renal histology indicated AIN; there was immune cell infiltration into the interstitium, tubulitis, and epithelial casts, although the glomeruli were largely intact. INTERVENTIONS: M charantia was discontinued and prednisolone was prescribed. OUTCOMES: The value of serum creatinine has almost been restored to the baseline level after 3 months. CONCLUSION: s: This is the first case report of AIN associated with the ingestion of a pure M charantia extract. Recognition of the possible adverse effects of these agents by physicians is very important for early diagnosis and appropriate management.

Spontaneous rupture of a renal artery pseudoaneurysm in a hemodialysis patient: A case report.

RATIONALE: Renal artery pseudoaneurysm is a rare vascular lesion usually caused by trauma or percutaneous urological procedures. Spontaneous rupture of pseudoaneurysms without predisposing events, especially in hemodialysis patients, has rarely been reported. PATIENT CONCERNS: A 25-year-old man receiving maintenance hemodialysis visited the emergency room because of sudden severe right flank pain. He had no history of trauma or urological procedures except for a left renal biopsy to diagnose Alport syndrome 10 years prior. DIAGNOSIS: Contrast-enhanced computed tomography revealed a right perirenal hematoma with pseudoaneurysms. INTERVENTIONS: On renal angiography, multiple pseudoaneurysms were observed in the right renal artery branches and embolization was performed. OUTCOMES: Post-angiography showed no pseudoaneurysms. His abdominal pain improved, and he was discharged 2 weeks after embolization. LESSONS: When maintenance dialysis patients complain of severe abdominal pain, spontaneous rupture of a renal pseudoaneurysm should be considered as a differential diagnosis, even if the patient has no history of trauma or previous urological procedures.

Paricalcitol Attenuates Contrast-Induced Acute Kidney Injury by Regulating Mitophagy and Senescence.

Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-acquired renal failure, with an incidence of 11%. However, the disease mechanism remains unclear, and no effective treatment is available. Paricalcitol has been reported to be effective in animal models of kidney injury. We hypothesized that paricalcitol could play a renoprotective role against CI-AKI. Rats were divided into control, paricalcitol, contrast, and paricalcitol-plus-contrast groups. We used a previously published protocol to produce CI-AKI. Paricalcitol (0.3 µg/kg) was administered intraperitoneally before 24 h and 30 min before indomethacin. We used HK-2 cells to evaluate the effects of paricalcitol on mitophagy and senescence. Ioversol triggered renal dysfunction, increasing blood urea nitrogen and serum creatinine. Significant tubular damage, increased 8-OHdG expression, and apoptosis were apparent. Ioversol injection induced high expression levels of the mitophagy markers Pink1, Parkin, and LC3 and the senescence markers ß-galactosidase and p16INK4A. Paricalcitol pretreatment prevented renal dysfunction and reduced tissue damage by reducing both mitophagy and senescence. Cellular morphological changes were found, and expression of LC3B and HMGB1 was increased by ioversol in HK-2 cells. Paricalcitol countered these effects. This study showed that mitochondria might drive injury phenotypes in CI-AKI, and that paricalcitol protects against CI-AKI by decreasing mitochondrial damage.

The effect of the type of anesthesia on the quality of postoperative recovery after orthopedic forearm surgery.

BACKGROUND: Although the quality of postoperative recovery may be affected by factors, there are few investigations whether the type of anesthesia also affects it. In this single-blinded, prospective, observational study, we compared the quality of postoperative recovery in patients undergoing orthopedic forearm surgery under general or regional anesthesia (brachial plexus block). METHODS: Ninety-seven subjects, aged 18-65 years and American Society of Anesthesiologists physical status I or II, undergoing orthopedic forearm surgery, were allocated to general or regional anesthesia group. The quality of postoperative recovery was assessed using a validated Korean version of Quality of Recovery-40 (QoR-40K) questionnaire. Patients were surveyed three times, the day before surgery (baseline) and 1st and 7th day after the surgery, and the scores of both groups were compared. RESULTS: We analyzed 47 and 50 patients in general and regional anesthesia, respectively. The global QoR-40K score and those of each of its five dimensions were not significantly different between the two groups at baseline, 1st and 7th day postoperatively. In two-way RM ANOVA, the global QoR-40K score at postoperative 1st day was significantly lower than that of baseline (P < 0.001) and postoperative 7th day (P < 0.001), respectively, in both general and regional anesthesia groups. However, there was no significant difference at each timepoint between the two groups. CONCLUSIONS: The present study suggests that brachial plexus block with intravenous dexmedetomidine infusion does not improve the quality of postoperative recovery compared to sevoflurane inhalation anesthesia with remifentanil infusion in patients undergoing orthopedic forearm surgery.

Clinical relevance of cell-free mitochondrial DNA during the early postoperative period in kidney transplant recipients.

Recent studies indicate that urinary mitochondrial DNA (mtDNA) is predictive of ischemic AKI and is related to delayed graft function (DGF) in renal transplantation. Nevertheless, the clinical implications and prognostic value of urinary mtDNA in kidney transplantation remain undetermined. Here, we aimed to evaluate the associations between cell-free mtDNA and clinical parameters, including pathological findings in allograft biopsy and post-transplant renal function. A total of 85 renal transplant recipients were enrolled, and blood and urine samples were collected at a median of 17 days after transplantation. Cell-free nuclear and mtDNA levels were measured by quantitative polymerase chain reaction for LPL and ND1 genes. Urinary cell-free mtDNA levels were significantly higher in patients with DGF (P < 0.001) and cases of deceased donor transplantation (P < 0.001). The subjects with acute rejection showed higher urinary mtDNA levels than those without abnormalities (P = 0.043). In addition, allograft functions at 9- and 12-month post-transplantation were significantly different between tertile groups of mtDNA independent of the presence of DGF or acute rejection, showing significantly better graft outcome in the lowest tertile group. Urinary cell-free mtDNA levels during the early post-transplant period are significantly associated with DGF, acute rejection in graft biopsy, and short-term post-transplant renal function.

Sex-related differences in the intratubular renin-angiotensin system in two-kidney, one-clip hypertensive rats.

The intratubular renin-angiotensin system (RAS) is thought to play an essential role in hypertensive renal disease, but information regarding sex-related differences in this system is limited. The present study investigated sex differences in the intratubular RAS in two-kidney, one-clip (2K1C) rats. A 2.5-mm clip was placed on the left renal artery of Sprague-Dawley rats, and rats were euthanized 3 or 5 wk after the operation. Systolic blood pressure increased in 2K1C rats in both sexes but was significantly higher in male rats than in female rats, and an antihypertensive effect was not observed in 2K1C ovariectomized (OVX) female rats. Compared with male 2K1C rats, intratubular angiotensin-converting enzyme (ACE) and ANG II were repressed, and intratubular ACE2, angiotensin (1-7), and Mas receptor were increased in both kidneys in female 2K1C rats 5 wk after surgery. Comparison with male and female rats and intratubular mRNA levels of ACE and ANG II type 1 receptor were augmented in OVX female rats, regardless of the clipping surgery 3 wk postoperation. ANG II type 2 receptor was upregulated in female rats with or without OVX; thus, the ANG II type 1-to-type 2 receptor ratio was higher in male rats than in female rats. In conclusion, female rats were protected from hypertensive renal and cardiac injury after renal artery clipping. An increase in the intratubular nonclassic RAS [ACE2/angiotensin (1-7)/Mas receptor] and a decrease in the ANG II type 1-to-type 2 receptor ratio could limit the adverse effects of the classic RAS during renovascular hypertension in female rats, and estrogen is suggested to play a primary role in the regulation of intratubular RAS components.

A case of bilateral leg edema associated with levofloxacin: A case report.

RATIONALE: A number of medicines are associated with edema. However, only 2 cases of edema of both lower legs, associated with levofloxacin, have been reported. PATIENT: We report the case of levofloxacin-associated bilateral leg edema in an 81-year-old male. The patient was referred to the Division of Nephrology due to edema limited to both lower legs, which had developed 1 day before. He had undergone supraglottic laryngectomy due to supraglottic cancer in our institution 6 months ago. He had been admitted to the Department of Otolaryngology due to persistent aspiration and general weakness 5 days ago. DIAGNOSIS: The patient had no underlying diseases that could result in edema. No abnormalities were detected in several diagnostic tests. He strongly denied using other medications including herbal or traditional remedies, recreational drugs, or drugs of abuse. The patient had been intravenously administered levofloxacin at 750 mg per day 5 days earlier; on this basis levofloxacin-induced edema was suspected. INTERVENTIONS AND OUTCOMES: Levofloxacin was immediately withdrawn and conservative management (salt restriction and withdrawal of intravenous fluid) was initiated. His edema was completely restored within 3 weeks after withdrawal of levofloxacin. OUTCOMES: The patient stopped taking levofloxacin and he did not have any recurrent edema until his death due to uncontrolled pneumonia. LESSONS: Levofloxacin should be added to the list of drugs associated with the development of bilateral leg edema. This might obviate the need for time-consuming studies for diagnostic purposes and application of ineffective or harmful treatments.

Combination therapy of low-dose cyclosporine and steroid in adults with IgA nephropathy
.

BACKGROUND: A few clinical trials in IgA nephropathy (IgAN) have shown that cyclosporine A (CyA) had therapeutic efficacy in reducing proteinuria. MATERIALS AND METHODS: This is a retrospective study, and all cases were selected based on kidney biopsy-proven IgAN. We reviewed the data of IgAN patients in the glomerulonephritis registry at Kyung Hee University Medical center and collected data on 86 patients with urinary protein/Cr ratio (PCR; g/g) > 0.5 and estimated GFR (eGFR) of > 50 mL/min/1.73m2 who were treated with combination therapy of low-dose CyA plus low-dose steroid (C+P; n = 37) and high-dose steroid single therapy (P; n = 49). RESULTS: In the C+P group, the mean duration of therapy was 14.5 ± 13.1 months, and the mean duration of follow-up 66.2 ± 36.3 months. In the C+P group, the urine PCR levels significantly declined after treatment (< 0.05). After 6 months of treatment, 12 (32%) patients were in complete remission and 7 (19%) in partial remission in the C+P group, compared with 21 (42%) and 11 (22%) in the P group, respectively. Urine PCR levels were also significantly reduced in 12 patients in the C+P group who had initial urine PCR between 0.5 and 1.0. The degree of hematuria was significantly reduced after treatment in the C+P group. These effects of C+P therapy on proteinuria and hematuria were very comparable to high-dose P therapy. After 2 years, a decline in renal function, > 25% decrease in eGFR from baseline levels, developed in 3 (8.1%) in the C+P group, compared with 4 (8.2%) in the P group. The rate of decline in renal function during follow-up was -0.14 ± 0.40 mL/min/1.73m2/month in the C+P group compared with -0.12 ± 0.22 mL/min/1.73m2/month in the P group. There were no changes of mean eGFR during the first 24 months, but the eGFR significantly decreased at last follow-up in both groups. When patients in the C+P group were divided into progressive (n = 9) and nonprogressive (n = 28) groups, a significant reduction in the amount of proteinuria after treatment was observed in the nonprogressive group, in contrast to the progressive group. In the C+P group, there were no severe adverse effects, especially no acute renal impairment, requiring discontinuation of CyA in this study. The incidence of infection was much lower in the C+P group than that in the P group. The limitation is that CyA acts to nonspecifically reduce proteinuria, so it requires long-term follow-up off CyA therapy for more than 2 years to determine. CONCLUSION: Our retrospective uncontrolled study provides only weak evidence that combination therapy of low-dose C+P could be an alternative to high-dose P therapy and be safe in adult IgAN patients with relatively normal renal function and proteinuria of > 0.5 g/g. Development of safe and effective therapy is still a major challenge requiring well-controlled prospective studies with this or other combination therapies.

Itraconazole Attenuates Peritoneal Fibrosis Through Its Effect on the Sonic Hedgehog Signaling Pathway in Mice.

BACKGROUND: Peritoneal fibrosis is a devastating complication of peritoneal dialysis. However, its precise mechanism is unclear, and specific treatments have not yet been established. Recent evidence suggests that the sonic hedgehog (SHH) signaling pathway is involved in tissue fibrogenesis. Drugs that inhibit this pathway are emerging in the field of anti-fibrosis therapy. Itraconazole, an anti-fungal agent, was also recently recognized as an inhibitor of the SHH signaling pathway. In this study, we used a mouse model to investigate whether the SHH signaling pathway is involved in the development of peritoneal fibrosis and the effects of itraconazole on peritoneal fibrosis. METHODS: Peritoneal fibrosis was induced by intraperitoneal (IP) injection of 0.1% chlorhexidine gluconate (CG) solution every other day for 4 weeks, with or without itraconazole treatment (20 mg/kg, IP injection on a daily basis). Male C57BL/6 mice were divided into 4 groups: saline group, saline plus itraconazole group, CG group, and CG plus itraconazole group. Isotonic saline was administered intraperitoneally to the control group. The peritoneal tissues were evaluated for histological changes, expression of fibrosis markers, and the main components of the SHH signaling pathway. RESULTS: Peritoneal thickening was evident in the CG group and was significantly decreased by itraconazole administration (80.4 ± 7.7 vs. 28.2 ± 3.8 µm, p < 0.001). The expression of the following SHH signaling pathway components was upregulated in the CG group and suppressed by itraconazole treatment: SHH, patched, smoothened, and glioma-associated oncogene transcription factor 1. The IP injection of CG solution increased the expression of fibrosis markers such as α-smooth muscle actin and transforming growth factor-ß1 in the peritoneal tissues. Itraconazole treatment significantly decreased the expression of these markers. CONCLUSION: Our study provides the first evidence that the SHH signaling pathway may be implicated in peritoneal fibrosis. It also demonstrates that itraconazole treatment has protective effects on peritoneal fibrosis through the regulation of the SHH signaling pathway. These findings suggest that blockage of the SHH signaling pathway is a potential therapeutic strategy for peritoneal fibrosis.

Observations of the Effects of Angiotensin II Receptor Blocker on Angiotensin II-Induced Morphological and Mechanical Changes in Renal Tubular Epithelial Cells Using Atomic Force Microscopy.

OBJECTIVE: Angiotensin II (Ang II) plays a profibrotic role in the kidneys. Although many pathways of Ang II have been discovered, the morphological and mechanical aspects have not been well investigated. We observed the changes in tubular epithelial cells (TECs) after Ang II treatment with or without Ang II receptor blockers (ARBs) using atomic force microscopy (AFM). METHODS: TECs were stimulated with Ang II with or without telmisartan, PD123319, and blebbistatin. AFM was performed to measure the cellular stiffness, cell volume, and cell surface roughness. Epithelial to mesenchymal transition markers were determined via immunocytochemistry. RESULTS: After Ang II stimulation, cells transformed to a flattened and elongated mesenchymal morphology. Cell surface roughness and volume significantly increased in Ang II treated TECs. Ang II also induced an increase in phospho-myosin light chain and F-actin and a decrease in E-cadherin. Ang II coincubation with either telmisartan or blebbistatin attenuated these Ang II-induced changes. CONCLUSION: We report, for the first time, the use of AFM in directly observing the changes in TECs after Ang II treatment with or without ARBs. Simultaneously, we successfully measured the selective effect of PD123319 or blebbistatin. AFM could be a noninvasive evaluating strategy for cellular processes in TECs.

Urinothorax after ultrasonography-guided renal biopsy: a case report.

BACKGROUND: Urinothorax is defined as the presence of urine in the pleural space and is a rather rare cause of transudate pleural effusion. The potential etiologies are urinary tract obstruction and trauma. Diagnosis requires a high index of clinical suspicion and the condition is completely reversible following relief of underlying disease. CASE PRESENTATION: We report a 27-year-old man who developed urinothorax after renal biopsy. Urine leakage was confirmed with 99mTc DTPA (diethylenetriaminepentacetate) and single-photon emission computed tomography scans and retrograde pyelography. The pleural effusion was completely resolved by removing the leakage with a Foley catheter and a double J stent. CONCLUSIONS: Urinothorax has not been reported in patients doing renal biopsy in the literature. Based on our experience, urinothorax should be suspected, diagnosed, and managed appropriately when pleural effusion occurred after renal biopsy.

Urinary exosomal viral microRNA as a marker of BK virus nephropathy in kidney transplant recipients.

OBJECTIVE: Bkv-miR-B1-5p, one of the microRNAs encoded by BK virus, was recently reported to be elevated in the blood among the patients with BK virus nephropathy (BKVN). Urinary exosome was suggested to be a possible source of biomarker for kidney diseases, but it was unknown whether it could contain viral microRNA as well as human microRNAs. The aim of this study was to evaluate whether urinary exosomal BK viral microRNA were expressed during replication and could be used to diagnose BKVN in kidney transplant recipients. MATERIALS AND METHODS: In a cross-sectional multicenter study, we collected and analyzed 458 graft biopsies from 385 kidney transplant recipients. Urine samples were collected at the time of graft biopsy, and microRNAs in urinary exosome were measured once. For 13 patients with BKVN and 67 age, sex-matched kidney transplant recipients, we measured BK viral microRNA B1-5p, 3p and human microRNA-16 in urinary exosomal fraction and compared the diagnostic value with BK viral load in plasma and urine. RESULTS: Pathology proven BKVN was diagnosed in 13 patients (2.8%). High levels of bkv-miR-B1-5p and bkv-miR-B1-3p were shown in all patients with BKVN. Meanwhile, plasma BK viral load assay (cut-off value of ≥ 4.0 log10 copies/mL) showed false negative in 3 cases and urinary BK viral load assay (cut-off value of ≥ 7.0 log10 copies/mL) showed false negative in 1 case among these 13 patients. The receiver operator characteristics curve analysis for bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 showed excellent discriminative power for the diagnosis of BKVN, with area under the curve values of 0.989 and 0.985, respectively. CONCLUSIONS: This study suggests that urinary exosomal bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 could be surrogate markers for the diagnosis of BKVN.

Renal Tubular Acidosis in Patients with Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) is characterized by lymphocytic infiltration of the exocrine glands resulting in decreased saliva and tear production. It uncommonly involves the kidneys in various forms, including tubulointerstitial nephritis, renal tubular acidosis, Fanconi syndrome, and rarely glomerulonephritis. Its clinical symptoms include muscle weakness, periodic paralysis, and bone pain due to metabolic acidosis and electrolyte imbalance. Herein, we describe the cases of two women with pSS whose presenting symptoms involve the kidneys. They had hypokalemia and normal anion gap metabolic acidosis due to distal renal tubular acidosis and positive anti-SS-A and anti-SS-B autoantibodies. Since one of them experienced femoral fracture due to osteomalacia secondary to renal tubular acidosis, an earlier diagnosis of pSS is important in preventing serious complications.

Clinicopathological features of diabetic and nondiabetic renal diseases in type 2 diabetic patients with nephrotic-range proteinuria.

Heavy proteinuria with or without features of nephrotic syndrome is associated with many primary and systemic diseases. For diabetic patients, distinguishing nondiabetic renal disease (NDRD) from diabetic nephropathy (DN) is important in choosing treatment modalities and determining renal prognosis. However, clinical relevance of heavy proteinuria is inconsistent with clinical DN assessments. This study investigated the clinicopathological features and renal outcomes of DN and NDRD in type 2 diabetic patients with nephrotic-range proteinuria.We enrolled 220 cases of type 2 diabetic patients who underwent renal biopsy. They were grouped according to the presence of nephritic-range proteinuria and pathological features. Baseline characteristics, laboratory findings, types of pathological diagnosis, and renal outcomes were analyzed in patients with heavy proteinuria.Upon kidney biopsy, 129 patients (58.6%) showed nephritic-range proteinuria. Patients with heavy proteinuria (an average urine protein-to-creatinine ratio of 10,008 ±â€Š7307 mg/gCr) showed lower serum albumin levels and higher total cholesterol levels, but did not show any difference in age, duration of diabetes, renal function, or the presence of retinopathy compared with those with mild-to-moderate proteinuria (an average urine protein-to-creatinine ratio of 1581 ±â€Š979 mg/gCr). Renal biopsy revealed that the prevalence of NDRD was 37.2% in patients with heavy proteinuria, which was significantly lower than that in patients with mild-to-moderate proteinuria (63.7%). The most common pathological types of NDRD were membranous nephropathy (41.7%), IgA nephropathy (14.6%), and minimal change disease (10.4%). NDRD patients showed lower prevalence of diabetic retinopathy and better kidney function irrespective of proteinuria. Immunosuppressive treatment was administered more frequently in patients with heavy proteinuria (56.3%) compared with patients with mild-to-moderate proteinuria (20%) because of the pathological differences according to the amount of proteinuria. Renal outcomes were significantly worse in patients with DN than in patients with NDRD.DN patients with heavy proteinuria exhibited different prevalence of NDRD and worse prognosis. Renal biopsy in type 2 diabetic patients should be more extensively considered to accurately diagnose NDRD, guide further management, and predict renal outcomes, especially in patients with nephrotic-range proteinuria.

Both absolute and relative quantification of urinary mRNA are useful for non-invasive diagnosis of acute kidney allograft rejection.

Urinary mRNA analysis with three-gene set (18S rRNA, CD3ε, and IP-10) has been suggested as a non-invasive biomarker of acute rejection (AR) in kidney transplant recipients using quantitative real-time PCR (qPCR). Application of droplet digital PCR (ddPCR), which has been suggested to provide higher sensitivity, accuracy, and absolute quantification without standard curves, could be a useful method for the quantifying low concentration of urinary mRNA. We investigated the urinary expression of these three genes in Korean patients with kidney transplantation and also evaluated the usefulness of ddPCR. 90 urine samples were collected at time of allograft biopsy in kidney recipients (n = 67) and from patients with stable renal function more than 10 years (n = 23). Absolute quantification with both PCR system showed significant higher mRNA levels of CD3ε and IP-10 in AR patients compared with stable transplants (STA), but there was no difference in 18S rRNA expression across the patient groups. To evaluate discrimination between AR and STA, ROC curve analyses of CTOT-4 formula yielded area under the curve values of 0.72 (95% CI 0.60-0.83) and 0.77 (95% CI 0.66-0.88) for qPCR and ddPCR, respectively. However, 18S normalization of absolute quantification and relative quantification with 18S showed better discrimination of AR from STA than those of the absolute method. Our data indicate that ddPCR system without standard curve would be useful to determine the absolute quantification of urinary mRNA from kidney transplant recipients. However, comparative method also could be useful and convenient in both qPCR and ddPCR analysis.