Hydralazine use can be associated with IgM-dominated immune complex-mediated glomerulonephritis.

CONTEXT: IgM-dominant immune complex-mediated glomerulonephritis (IgM-dominant ICMGN) is a rare renal entity, characterized by a membranoproliferative pattern by light microscopy, dominant IgM staining by immunofluorescent staining, and subendothelial deposits by electron microscopy. This study was to investigate if some of IgM-ICMGN were associated with autoimmune disorders induced by hydralazine. DESIGN: Seven IgM-dominant ICMGN cases were identified over 8 years. Their pathologic phenotypes and clinical scenarios were analyzed in detail. RESULTS: Patients' ages ranged from 47 to 87 years old with 5 women and two men. Six of seven patients had drug-induced autoimmune phenomenon (hydralazine-induced positive ANCA and ANA). All of them had renal dysfunction and some proteinuria. Most pathologic features showed a membranoproliferative pattern of glomerulonephritis with dominant IgM deposits at subendothelial spaces. IgM nephropathy (a variant of focal segmental glomerulosclerosis), chronic thrombotic microangiopathy, and cryoglobulinemic glomerulopathy were ruled out in the cases. CONCLUSION: The hydralazine-induced autoimmune phenomenon can be seen in IgM-dominant ICMGN, which should be classified as a subtype of membranoproliferative glomerulonephritis.

Punctate IgG staining particles localize in the budding ballooning clusters of reactive foot processes in minimal change disease.

The etiology of minimal change disease (MCD) remains a mystery as the only characteristic findings are the diffuse effacement of foot processes seen on electron microscopy (EM). Punctate IgG staining found floating outside glomerular capillary loops in MCD cases was recently identified as autoimmune antibodies against nephrin of podocytes. We hypothesized that the punctate IgG staining is located on budding ballooning clusters (BBC) of reactive foot processes in Bowman's space found on EM. We identified seven patients with MCD cases showing IgG staining that were subsequently evaluated for BBC on EM. We concurrently examined 12 negative controls, either unremarkable cases or tubulointerstitial diseases, by EM. Immunogold labeling was performed to confirm the presence of IgG and determine localization. In seven MCD cases, there were positive punctate IgG staining particles outside of the glomerular basement membranes (GBM) along with concurrent punctate staining for C3, kappa, and lambda. By EM, all seven (100%) MCD cases revealed BBC that was characterized by ballooning foot processes ranging from 1 to 6 µm and was either budding or detached from the GBM in 3-7 clusters; no electron-dense materials were seen in BBC. BBC was also seen in only 1 of 12 (8%) negative controls. Immunogold labeling identified IgG particles within BBC of MCD by EM, but not in the negative control. Our data suggest that BBC are EM structures of reactive foot processes that are most likely correlated with punctate IgG staining seen in cases of MCD, supported by immunogold labeling for IgG.

Proteinuria in thrombotic microangiopathy is associated with partial podocytopathy.

BACKGROUND: Thrombotic microangiopathy (TMA) results in acute kidney injury, but the cause of heavy proteinuria in this disorder is puzzling. The goal of this study was to determine if there were significant effacement of foot processes and CD133-positive hyperplastic podocytes in TMA to explain the proteinuria. METHODS: The study included 12 negative controls (renal parenchyma removed from renal cell carcinoma) and 28 thrombotic microangiopathy due to different etiologies. The percent of foot process effacement was estimated, and proteinuria level was obtained for each TMA case. Both groups of cases were stained for CD133 by immunohistochemical method, and the number of positive CD133 in hyperplastic podocytes was counted and analyzed. RESULTS: Nineteen (19) of 28 (68%) TMA cases had nephrotic range proteinuria (urine protein/creatinine >3). Twenty-one (21) of 28 (75%) TMA cases showed positive CD133 staining in scattered hyperplastic podocytes within Bowman's space but was absent in control cases. The percent of foot process effacement (56 ± 4%) correlated with proteinuria (protein/creatinine ratio 4.4 ± 0.6) (r = 0.46, p = .0237) in TMA group. CONCLUSION: Our data indicate that the proteinuria in TMA can be associated with significant effacement of foot processes. CD133-positive hyperplastic podocytes can be seen in the majority of TMA cases of this cohort, indicating a partial podocytopathy.

Podocytopathies related to either COVID-19 infection or its vaccination, our experience and literature review.

Coronavirus disease 2019 (COVID-19) affects several organs including the kidney resulting in acute kidney injury (AKI) and variants of podocytopathies. From the beginning to the middle period of the COVID-19 pandemic, we have collected eight renal biopsies with various renal diseases including 4 podocytopathies. In addition, from the middle period to the near end of the COVID-19 pandemic, we have seen two of the patients who developed nephrotic syndrome following COVID-19 vaccination. Three of 4 podocytopathies were collapsing glomerulopathy (also called collapsing focal segmental glomerulosclerosis) and the fourth was a minimal change disease (MCD). Two of three collapsing glomerulopathy were found in African American patients, one of who was tested positive for having the high-risk allele APOL-1 G1. In addition, the two renal biopsies showed either MCD or replaced MCD following COVID-19 vaccination. MCD can be a rare complication following COVID-19 infection and COVID-19 vaccination, raising the question if there are similar antigens induced by the infection or by the vaccination that trigger the MCD. This article reports our experience of diagnosing podocytopathies related to either COVID-19 infection or its vaccination and provides a literature review regarding the incidence and potential pathophysiology in the field.

Resolving primary membranous glomerulopathy (MGN) reveals a dynamically metabolic pathway from sub-epithelium to glomerular basement membranes.

In idiopathic (primary) membranous glomerulopathy (MGN), there is a phenomenon of subepithelial deposits (stages 1 and 2) transitioned to intramembranous deposits, with lucent resolving features (stages 3 and 4). This phenomenon has not been described in other types of immune complex mediated glomerulonephritis with either subendothelial or mesangial deposits. The goal of this study was to evaluate what unique immunostaining pattern could occur in primary MGNs with intramembranous resolving features. PLA2R and IgG4 immunostains were performed in 50 primary MGNs, and 39 secondary MGNs after the clinical history was reviewed. Primary MGNs with resolving features were further evaluated in detail. A total of 84% (42/50) of primary MGN cases had diffuse positive immunostaining for IgG4 in the glomeruli, and most of them were also positive for PLA2R staining. Eight of the remaining primary MGN cases (8/50) with positive PLA2R but negative IgG4 staining in the glomeruli had diffuse resolving features as observed by electron microscopy. All secondary MGNs were stained negatively for both IgG4 and PLA2R except for one case with positive IgG4 staining but negative staining for PLA2R. Our data indicate that IgG4 staining on paraffin tissue is a very reliable screening tool to confirm the presence of primary MGN. Primary MGN with PLA2R+/IgG4- stains were seen in those with intramembranous resolving features. This finding is consistent with the known weak-binding capacity of IgG4 to the glomerular basement membranes. The transitional phenomenon from PLA2R+/IgG4+ subepithelial deposits to PLA2R+/IgG4- intramembranous resolving deposits in primary MGN implies that there may be a continuous metabolic activity from podocyte to glomerular basement membrane.

Myeloperoxidase immunohistochemical staining can identify glomerular endothelial cell injury in dense deposit disease.

BACKGROUND: Previous studies have demonstrated residual complement-mediated deposits in repeat kidney biopsies of C3 glomerulopathies (C3G) (dense deposit disease (DDD) and C3 glomerulonephritis) following eculizumab treatment, despite some clinical improvement. With residual complement deposition, it is difficult to determine whether there is a reduced complement-mediated endothelial cell injury. We validated that myeloperoxidase (MPO) immunohistochemical staining identified glomerular endothelial cell injury in crescentic glomerulonephritis and C3G. CASE (DIAGNOSIS/TREATMENT): We report that MPO staining in the glomerular endothelium of the post-treatment kidney biopsy was significantly reduced after 3 years of eculizumab treatment and clinical improvement in a 5-year-old boy with initial DDD and secondary crescent formation. CONCLUSION: We find that immunostaining for MPO is a useful method to compare glomerular endothelial injury in C3G following eculizumab treatment. This finding also supports the notion that eculizumab, a C5 blocker, may not mainly block C3 deposits in the glomeruli but significantly blocks final activation of the complement cascade, thus reducing glomerular endothelial cell injury.

Electron microscopic findings can support multiple etiologies of nephrotoxicity in renal tubules.

Electron microscopy (EM) has been mainly used for identifying ultrastructural abnormalities such as fusion of foot processes and immune complex deposits in glomeruli. However, electron microscopic findings in renal tubules can provide either diagnostic evidence (unique finding) or supportive evidence (additional finding) for final diagnosis. Here we present multiple situations that EM can be used for drawing conclusions of various drug-associated nephrotoxicity. Multiple cases with drug-induced nephrotoxicity are reviewed, including clinical history, EM findings, and serum creatinine (sCr) levels, prior to renal biopsy and during follow-up. Two cases with nephrotoxicity by aminoglycoside antibiotics showed acute tubular injury with EM findings of myeloid bodies, characterized by laminated dense materials in lysosomes in both proximal and distal tubular epithelium (diagnostic evidence). Five cases of vancomycin associated nephrotoxicity presented with acute tubular injury and vancomycin casts in distal tubules, characterized by central laminated casts in the lumina of distal tubules (supportive evidence). Vedolizumab, a humanized monoclonal antibody used in treating Crohn's disease, can cause T-cell dominant acute interstitial nephritis, with EM revealing lymphocytic infiltration into tubules as tubulitis (supportive evidence). Four of Seven cases (5/8) cases had renal functional recovery upon follow-up check for sCr. EM findings of characteristic changes in renal tubules can be particularly useful as either diagnostic or supportive evidence, in correlation with clinical history and etiologies of nephrotoxicity. Therefore, EM should not only focus on glomerular changes, but renal tubular changes as well.

Clear cell renal cell carcinoma cells show diffuse expression of phagocytotic markers through the identification of lysosome-rich eosinophilic granules.

BACKGROUND: Paneth cell-like granules (PCLG) in clear cell renal cell carcinomas (RCC) have previously been reported but were not found to express neuroendocrine markers. This study was to investigate if the eosinophilic granules (so called PCLG) were enlarged lysosomes. METHODS: A retrospective review of 72 different renal tumors was conducted which included 42 clear cell RCC, 16 papillary RCC, 6 chromophobe RCC, 5 clear cell papillary RCC, 2 urothelial carcinomas and 1 unclassified RCC. All tumors were evaluated for the eosinophilic granules on hematoxylin and eosin-stained sections. In addition, PAS-D staining, immunohistochemical stains, and electron microscopy were performed. RESULTS: The eosinophilic granules were found in 19% (8 out of 42) clear cell RCC, but not in the other renal tumor types. The granules stained positively for PAS-D and were also positive for lysosomal protein markers CD68 and lysozyme. Electron microscopy revealed that the eosinophilic granules were smooth ball-shaped structures in the cytoplasm, ranging in size from 0.8 to 1.4 µm. The overall findings indicate that the eosinophilic granules were best correlated with lysosomes. CONCLUSIONS: The eosinophilic granules in clear cell RCC are expanded lysosomes, and this may be used as a unique feature for confirming the pathologic diagnosis of clear cell RCC. The findings further support the view that clear cell RCC have phagocytic capacity due to their containing abundant lysosomes in the cytoplasm.

The Role of Bone Marrow Biopsy Evaluation in the Workup for Monoclonal Gammopathy of Renal Significance: A Diagnosis of Exclusion.

CONTEXT.­: Monoclonal gammopathy of renal significance (MGRS) is a relatively new concept for patients with renal monoclonal protein deposition (RMPD) (except monoclonal cast nephropathy) and has been used as a reason for nephrologists to obtain a bone marrow biopsy (BMB). It takes a team of pathologists and clinicians to determine when RMPD at our institution can be defined as MGRS. OBJECTIVE.­: To identify the proportion of various subtypes of tentative MGRS diagnosed by renal biopsy that can be confirmed as final MGRS after BMB. DESIGN.­: One hundred thirty kidney biopsies with variants of RMPD were identified during the past 10 years. Biopsy cases with known myeloma, B-cell lymphoma, or monoclonal cast nephropathy were separated as a heavy-burden group. The remaining biopsies with RMPD were considered tentative MGRS. Their BMB and clinical indices were further analyzed to determine the final percentage of MGRS diagnoses. RESULTS.­: Among the 130 renal paraprotein deposition cases, 44 (33.8%) were categorized as the heavy-burden group. In the remaining 86 cases, 33 (38.4%) with subsequent identification of myeloma (>10% of monoclonal plasma cells) or lymphoma in BMB were further considered as heavy-burden cases. Eighteen cases (18 of 86; 20.9%) did not receive follow-up BMB; thus, no further analysis was performed. BMBs diagnosed as either nonmalignant (no plasma cells; 8 of 86 cases; 9.3%) or premalignant (<10% plasma cells; 27 of 86 cases; 31.4%) were confirmed to be final MGRS (35 of 86; 40.7%). CONCLUSIONS.­: The data indicate that BMB is an important element in the confirmation of MGRS.

Malignant Tumors Identified in Adult Polycystic Kidney Disease Can Be Derived from Both Proximal Tubular and Distal Tubular Origins.

Adult polycystic kidney disease (APKD) is a genetic disorder leading to premature renal dysfunction and failure. The prevalence of malignant renal tumors occurring in the APKD setting has been rarely reported. OBJECTIVE: To better characterize malignant renal tumors in nephrectomy specimens of APKD and apply modern pathologic evaluation. METHODS: We reviewed our database of APKD specimens over the past 11 years (from 2012 to 2023) for primary malignant tumors within the kidneys of APKD. RESULTS: Of 48 nephrectomy specimens with APKD evaluated, 10 malignant renal tumors were identified, indicating a prevalence of 20.8 % (10/48). These included three clear cell (cc) renal cell carcinomas (RCC) (ranging from 1 mm to 6.7 cm), three papillary RCCs (2.5, 3.5, and 14 cm with lymph node metastasis), two cases of clear cell papillary (CCP) RCC, one acquired cystic disease (ACD) with associated RCC (4 mm), and one urothelial adenocarcinoma. The urothelial adenocarcinoma was found near a tubulovillous adenoma in a collecting duct and stained positively for GATA3 and Uroplakin-2 but was negative for PAX8 & CDX2. The tumor showed extensive invasion into perirenal fatty tissue and the rectum. Next generating sequencing (NGS) analysis of the tumor showed mutations in TERT, RB1, TP53, ERBB2, and TET1 genes, further supporting its urothelial origin. CONCLUSIONS: We found a prevalence of 20.8%, which was higher than in previous reports of malignant renal tumors in patients who underwent resections for APKD. Renal tumors were mostly from damaged proximal tubular origins (clear cell or papillary RCC), but less commonly were from distal tubular or urothelial cells as well (clear cell papillary RCC and urothelial adenocarcinoma).

Myeloperoxidase Staining Identifies Endothelial Injury of Peritubular Capillaries and Glomeruli in Renal Antibody-Mediated Rejection.

OBJECTIVE: It remains unclear if C4d staining is related to any peritubular and glomerular injury during antibody mediated rejection (ABMR). The goal of this study was to determine if myeloperoxidase (MPO) staining can highlight endothelial injury in peritubular capillaries (PTC) and glomeruli. METHODS: The study included 12 native negative controls, 19 transplant biopsies with borderline changes (BC) as transplant controls, and one group of renal transplant biopsies with ABMR as the study group (acute/chronic, n=22). All three groups were stained for MPO immunohistochemically, and the MPO expressions in the endothelium of PTC and glomeruli were evaluated and correlated with serum creatinine (SCr). In addition, the ultrastructural layers of the PTC (an index for chronic allograft rejection) were correlated with MPO indices in PTC. RESULTS: The negative control group and the transplant controls showed no MPO expression in the endothelium of glomeruli and PTC. However, in the biopsies with ABMR, there were MPO-positive stains in the endothelial cells of glomeruli (15/21 cases, 71.4 %) and PTC (16/22 cases, 72.7 %). There were significant correlations between the peritubular MPO staining versus SCr (r=0.355 and p=0.0106) and glomerular MPO staining versus SCr (r=0.365 and p=0.0092). Furthermore, the layers of PTC by electron microscopy were significantly correlated with MPO scores in PTC (r=0.696, p=0.0001). CONCLUSION: Our data suggest that the MPO-positive endothelial injuries are most likely the cause leading to renal graft dysfunction following ABMR.

Role of progenitor cell marker CD133 in supporting diagnosis of collapsing glomerulopathy.

PURPOSE: A previous immunofluorescent study suggests that, in collapsing glomerulopathy, most hyperplastic podocytes that stained positively for a progenitor cell marker CD133 are derived from CD133 + parietal epithelial cells. In pathology practice, not all renal biopsies with collapsing glomerulopathy show the typical morphologic features for this entity, which include florid podocyte hyperplasia, collapsing glomerular capillary loops, and cystic tubular dilation. This study was made to determine if CD133 staining using an immunohistochemical method can be used to confirm hyperplastic podocytes and identify extensive acute tubular injury in collapsing glomerulopathy. METHODS: Twenty-one collapsing glomerulopathy biopsies were stained for CD133 and compared with 15 biopsies with focal segmental glomerulosclerosis, not otherwise specified (FSGS). RESULTS: All patients with collapsing glomerulopathy were of African American descent with prominent renal failure and nephrotic range proteinuria. In contrast, the FSGS group consisted of patients from a variety of ethnic backgrounds with nephrotic range proteinuria but relatively low serum creatinine. The striking finding was that all collapsing glomerulopathy cases showed positive CD133 staining in the clusters of hyperplastic podocytes. There was significantly higher CD133-positive staining rate for hyperplastic podocytes (38%) in the glomeruli of the collapsing glomerulopathy group when compared to small clusters of hyperplastic podocytes in the FSGS group (8%). In addition, when compared to the relatively weak CD133 staining in the proximal tubules of the FSGS group, the proximal tubules of the collapsing glomerulopathy group all showed diffuse and strong CD133 staining as a feature of severe acute tubular injury, which corresponded to the high serum creatinine levels in these patients. CONCLUSION: Our data indicate that the combination of the distinctive mosaic CD133 staining in hyperplastic podocytes and the diffuse tubular CD133 staining is helpful in supporting a diagnosis of collapsing glomerulopathy.

Focal Segmental Glomerulosclerosis (FSGS) Progressing to Collapsing Glomerulopathy in Renal Transplant Recipients With and Without COVID-19 Infection.

BACKGROUND: Collapsing glomerulopathy (CGN) secondary to HIV or COVID-19 infection mainly occurs in patients of African American descent due to APOL-1 gene mutations, but CGN is occasionally reported in white patients. CGNs are rarely reported in renal transplant biopsies and their association with idiopathic focal segmental glomerulosclerosis (FSGS) is unclear. METHODS AND RESULTS: Patient #1 was a 48-year-old Caucasian white man who had a renal transplant 8 years ago and was recently diagnosed with COVID-19 infection. Two weeks post infection, his serum creatinine (SCr) increased to 2.01 mg/dL from a baseline of 1.40 mg/dL, and he developed concomitant nephrotic range proteinuria. The first renal transplant biopsy showed FSGS. Four weeks later, his sCr level increased to 2.65 mg/dL with worsening proteinuria, and a second renal transplant biopsy revealed CGN. Patient #2 was a 32-year-old African American man whose native renal biopsy revealed primary FSGS. He received a renal transplant with initial post-transplant sCr level at 1.17 mg/dL. Four months later, his sCr and protein-to-creatinine ratio began to rise. Sequential biopsies revealed that the patient had developed recurrent FSGS, which progressed to show features of CGN. The CGN was further confirmed in his transplant kidney graft at autopsy later. CONCLUSIONS: This is the first case report of CGN in a white renal recipient with COVID-19 infection. The pathologic presentations of FSGS progressing to collapsing FSGS in our 2 renal transplant recipients suggest that FSGS and GGN may share a common pathophysiologic mechanism of podocytopathy.

Pathologic Correlation with Renal Dysfunction after Intravitreal Injections of Vascular Endothelial Growth Factor Antagonists.

OBJECTIVE: Vascular endothelial growth factor (VEGF) antagonists have been used for treating metastatic neoplasms. It has also been known that one of its side effects is to cause proteinuria and renal failure in the setting of thrombotic microangiopathy (TMA). The underlying mechanism is likely due to the inhibition of VEGF production in podocytes, resulting in diffuse fusion of foot processes and impaired glomerular endothelial fenestrations, and leading to massive proteinuria and subsequent glomerular endothelium injury. Intravitreal injection of VEGF antagonists (IIVA) has been also used to treat macular degeneration and diabetic retinal neo-vascular proliferation. The majority of patients tolerate the treatment well. However, IIVA can lead to renal dysfunction including proteinuria and gradual renal failure as a rare side effect. The goal of this study was to report two cases related to the nephrotoxicity of IIVA and review the literature associated with this topic. CASE REPORT: The first diabetic patient had elevated serum creatinine at 3.25 mg/dl and proteinuria/creatinine ratio at 6.1 after 48-month treatment of IIVA. The first renal biopsy revealed thrombotic microangiopathy that was correlated with his increased serum creatinine and nephrotic range of proteinuria. The second diabetic patient had increased serum creatinine up to 1.89 mg/dl but low proteinuria. The second biopsy showed acute tubular necrosis that was correlated with his elevated serum creatinine. CONCLUSION: Intravitreal injection of VEGF antagonist can be associated with thrombotic microangiopathy and acute tubular necrosis, leading to renal dysfunction.

The clinical features of overlap syndrome (ANCA-associated crescentic glomerulonephritis [AACGN] and immune complex-mediated glomerulonephritis) are similar to those of AACGN alone.

The overlap syndromes of anti-neutrophil cytoplasmic antibodies (ANCA)-associated crescentic glomerulonephritis (AACGN) and variants of immune complex medicated glomerulopathy (ICMGN) have been reported. But very few have compared AACGN alone with the overlap syndromes (AACGN plus ICMGN). The aim of this retrospective study was to make that comparison, following serum creatinine (sCr) to determine whether the two groups (AACGN-only group versus overlap group) would behave differently over time. We identified 14 cases with dual diagnoses of AACGN and various ICMGN in the overlap group. Data were collected and compared with 15 randomly selected AACGN-only cases over the similar period of time. The overlap syndrome represented 0.35% of our overall biopsies (14/4049). All 14 patients were ANCA positive and had crescentic formation. The percentage of crescents in the biopsies ranged from 10 to 78%. ICMGN included the following: membranoproliferative glomerulonephritis, post-infectious glomerulonephritis, membranous glomerulopathies, idiopathic mesangial proliferative glomerulonephritis, lupus nephritis, and IgA nephropathy. With the exception one biopsy revealing lupus nephritis class III, most of the ICMGN were mild. When compared to the AACGN-only group, there were no significant differences in clinical and histologic indices including age, percent of crescents, and sCr (on biopsy days, and over the follow-up periods), although the numbers of follow-up cases were limited over time. Our findings suggest that AACGN was the dominant disease process in the majority of overlap syndromes between AACGN and ICMGN, similar to the clinical processes of AACGN-only disease, therefore, the AACGN in overlap syndrome cases should be the main target for clinical management.

Monoclonal Gammopathy of Renal Significance and its Associated Experimental Models.

Monoclonal gammopathy of renal significance (MGRS) is a state of circulating monoclonal immunoglobulin (Ig) and light chains that cause kidney injury without definite evidence of multiple myeloma (MM). Although chemotherapy is used to treat many variants of MGRS and has been recently recommended, relatively limited clinical validation studies are available. A few transgenic models of MM reveal renal deposition of monoclonal Ig and light chains. We have demonstrated that the XBP1s-transgenic mouse model from early plasma cell dyscrasia to MM reveals monoclonal IgG/kappa deposition at the subendothelial spaces of the glomeruli, mimicking proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Inhibition of a key immune-modulator, gp96/grp94, genetically or pharmacologically results in a significant reduction of plasma cells within the bone marrow and reduced renal deposition of monoclonal IgG and kappa light chain. This article will review the emerging role of in vitro and animal models from plasma cell dyscrasia to MM in understanding the renal deposition of monoclonal Ig and light chains, along with its potential treatment strategies.

Kidney injury molecule-1, a sensitive and specific marker for identifying acute proximal tubular injury, can be used to predict renal functional recovery in native renal biopsies.

Kidney injury molecule-1 (KIM-1) staining has been shown to be very useful in identifying acute proximal tubular injury, but its sensitivity, specificity and predicting values for the recovery of renal function after injury in renal biopsies have not been well established. In the first study, we randomly selected 184 renal biopsies from a wide age range of patients (children to elderly) with various renal diseases. KIM-1 staining scores were significantly correlated with serum creatinine (sCr) levels (P < 0.05) in all age groups. Receiver-operating characteristic curve (ROC) was generated to evaluate true-positive rate (sensitivity) and true-negative rate (1-specificity). The area under the curve (AUC) in pediatric cases was 0.74, which demonstrated KIM-1 was a fair index in correlating with sCr. In adults, the AUC was 0.87, indicating that KIM-1 was an even better index in the adult population in correlating to sCr. The second study was to determine whether KIM-1 could be a potential predictor of the recovery of acute kidney injury (AKI), and 51 indicated native biopsies with acute tubular injury were randomly selected for KIM-1 staining and sCr follow-up over a 6-month period. A higher KIM-1/sCr ratio (0.57 ± 0.06) was significantly and positively associated with a better reduction in sCr over 6 months. In summary, our data demonstrated that KIM-1 staining in renal biopsies is a sensitive and specific marker to identify acute tubular injury and KIM-1/sCr ratio is useful for predicting the recovery of renal function after injury, although some patients' sCr levels cannot return to their baseline levels.

Bilateral Testicular Infarction from IgA Vasculitis of the Spermatic Cords.

A 51-year-old man with type 2 diabetes mellitus and chronic obstructive pulmonary disease presented to the emergency room with increasing bilateral leg pain, rash, and scrotal swelling with pain. Skin biopsy from his thigh revealed IgA-associated vasculitis. Due to hematuria, a renal biopsy was performed and showed an IgA glomerulonephritis with focal fibrinoid necrosis and neutrophil accumulation. Bilateral orchiectomies were performed in two separate procedures ten and thirteen days after the renal biopsy, as a result of uncontrolled abscess formation in testicles. Microscopically, both testicles revealed large abscess formation destroying almost the entire testicular parenchyma without tumor cells. Spermatic cord margins were further scrutinized microscopically to show bilateral vasculitis in many small size vessels, confirmed by positive endothelial staining for IgA. Some of the affected arteries revealed central organizing thrombi with recanalization features, highly suggestive of vasculitis-associated thrombi formation, resulting in testicular ischemic infarction and abscess formation. We conclude that this adult patient developed a severe form of Henoch-Schönlein purpura, with vasculitis affecting multiple organs, including the most serious and unusual complication of bilateral testicular infarction.

Hodgkin's lymphoma with exuberant granulomatous reaction.

We report a 36-year-old woman, presented with cervical lymphadenopathy and low-grade fever. Two fine needle aspiration cytology and one excisional biopsy were performed in the referral hospital, all showed granulomatous lesions without necrosis. A tentative diagnosis of tuberculosis was made, and she started on antituberculous treatment. However, there was no clinical improvement. She presented to our institution one year after the initial diagnosis, and a new biopsy from the cervical lymph node revealed effacement of the whole node by marked non-necrotizing granulomatous reaction. However, there were scattered large cells with few classic Reed-Sternberg cells between the granulomas. Immunohistochemistry reveals strong reaction of CD15 and CD30, and negative staining for CD45RB, CD45RO, and CD20. These findings confirmed the diagnosis of Hodgkin's lymphoma with remarkable granulomatous reaction that almost masked the malignant component. She was treated with chemotherapy, and she showed an excellent response.