Jorge Isaac

Cast Nephropathy in a Case of Waldenström’s Macroglobulinemia

Waldenström’s macroglobulinemia is a low-grade lymphoplasmacytic lymphoma characterized by a circulating monoclonal IgM. The clinical manifestations are due to deposition of IgM in liver, spleen, and/or lymph nodes. Related symptoms include anemia and complications of the hyperviscosity syndrome. Renal involvement in classical cases of Waldenström’s macroglobulinemia is rare, and the pathological hallmark finding in the renal biopsy specimen is a thrombotic microangiopathy. We report the case of a 73-year-old female with the diagnosis of pernicious anemia for 2 years before she presented with acute renal failure. A renal biopsy performed suggested the diagnosis of myeloma cast nephropathy. However, bone marrow biopsy specimens and hematological studies did not support this diagnosis. Serum and urinary protein electrophoresis revealed a monoclonal lambda subtype IgM. Ultrasound imaging showed an enlarged spleen. The diagnosis of cast nephropathy in a patient with Waldenström’s macroglobulinemia was made. She underwent treatment with fludarabine and plasmapheresis/hemodyalisis with dramatic improvement of her renal function.

De Novo C1q Nephropathy in the Renal Allograft of a Kidney Pancreas Transplant Recipient: BK Virus-Induced Nephropathy?

C1q nephropathy is a distinct entity characterized by extensive and dominant C1q mesangial deposition with associated steroid resistant proteinuria in the absence of systemic lupus erythematosus. Several morphological patterns ranging from very subtle glomerular alterations to focal/segmental glomerulosclerosis and mesangial proliferative changes have been described. Interstitial nephritis secondary to BK polyomavirus is a recently recognized complication in kidney transplant recipients. It may be associated with a tubulitis-like picture, mimicking sometimes acute tubular rejection. We report the case of a kidney pancreas transplant recipient who developed de novo C1q nephropathy, in the setting of BK polyomaviral interstitial nephritis. He presented with renal allograft dysfunction and a kidney biopsy was performed. It was interpreted as acute cellular rejection. C1q deposits were detected by immunofluorescence studies and electron microscopy. The patient did not respond clinically to appropriate anti-rejection treatment and a second renal biopsy was performed. The possibility of an interstitial nephritis secondary to BK polyomavirus mimicking rejection was suggested. Special immunohistochemical and blood/urine PCR studies for BK virus were performed, confirming the diagnosis of BK virus tubulonterstitial nephritis with a persistent, probable BK virus induced C1q nephropathy.

Extent of glomerular tubularization is an indicator of the severity of experimental acute kidney injury in mice

Background: Acute kidney injury (AKI) secondary to ischemia continues to be a major clinical problem due to its high morbidity and mortality, and limited treatment options. Animal models are critical to both the study of the pathophysiology of AKI and the development of new interventions. Although histological changes at the glomerulotubular junction have been described in AKI, we examined here whether the extent of glomerular tubularization correlates with the degree of renal insufficiency in this condition. Methods: Groups of mice with ischemia/reperfusion AKI were utilized in which the severity of renal insufficiency was defined. The resulting level of glomerular tubularization was analyzed, and the involved cell type was identified by immunohistochemistry and electron microscopy. Results: The extent of glomerular tubularization increased significantly with the degree of renal insufficiency. Low level glomerular tubularization was present in normal mouse kidneys, while it was more common and increasingly circumferential in mice with more severe loss of kidney function. The parietal monolayer of cuboidal cells in glomeruli was contiguous with proximal tubular cells, showing a well-developed luminal brush border and positive staining for proliferating cell nuclear antigen and Lotus tetragonolobus, a proximal tubular cell-specific lectin. Conclusion: Increased levels of glomerular tubularization represent a poorly understood response to ischemic AKI in mice. As such, this glomerular ‘tubularization score’ may be useful to complement standard injury scores in experimental and, if detected, in clinical AKI.

Amelioration of Acute Renal Failure by Stem Cell Therapy—Paracrine Secretion Versus Transdifferentiation into Resident Cells Administered Mesenchymal Stem Cells Protect against Ischemic Acute Renal Failure through Differentiation-Independent Mechanisms. Am J Physiol Renal Physiol E-pub February 15, 2005

Although the kidney has been suspected, though not definitively proven, to contain organ-specific pluripotent stem cells, their role in regeneration after renal injury is uncertain ([1][1]–[3][2]). Recently, however, several investigators found evidence for a renoprotective role of non–organ-

De novo fibrillary glomerulopathy in the renal allograft of a patient with systemic lupus erythematosus

Lupus glomerulonephritis is a complication of systemic lupus erythematosus, with 10% of the patients developing end-stage renal disease. It is accepted that lupus patients are good candidates for kidney transplantation and that the disease activity is subdued after transplantation due to rigorous immunosuppression, with a low rate of graft loss due to recurrent glomerulonephritis. While recurrent fibrillary glomerulopathy has been reported in renal allografts, de novo disease has not. We report a patient with systemic lupus who underwent a renal transplantation and subsequently lost her allograft due to de novo fibrillary glomerulopathy. Four years after her first kidney transplant, the patient presented with acute deterioration of her renal function. A renal biopsy was performed, and it revealed a focal mesangioproliferative pattern with positive amorphous mesangial immunofluorescence staining for IgG and C3. Congo red staining was negative. Electron microscopy demonstrated the presence of randomly oriented nonamyloid fibrils in the mesangiun. The diagnosis of de novo fibrillary glomerulopathy was made. The patient lost her allograft and received a second cadaveric renal transplant 1 year later. She has had a stable renal function since then.

Renal Biopsy as a Primary Diagnostic Tool in Plasma Cell Dyscrasias

Renal alterations are common in patients with multiple mycloma. They are caused by the effects of abnormal circulating light chains on different renal compartments. Nodular mesangial expansion can be seen in light chain deposition disease, amyloidosis, diabetic nephropathy, and membranoproliferative glomerulonephritis. However, the pathologic mechanisms responsible for the mesangial expansion in these entities are different. Renal biopsies should be evaluated using a combination of histochemical stains (hematoxylin and eosin, periodic acid-Schiff, methenamine silver, trichrome, and Congo red) to attempt to characterize the mesangial alterations found in these cases. Although this battery of stains provides valuable information to formulate a preliminary diagnosis, often additional studies are necessary to confirm or to arrive at the precise diagnosis, including immunofluorescence and electron microscopy. Staining for kappa and lambda light chains should be done routinely to detect monoclonal light chain-related renal diseases. This review focuses on mesangiopathic alterations observed in light chain deposition discase and AL-amyloidosis (light chain-related), and presents a rational approach to differentiate these entities from similar mesangial alterations seen in other glomerulopathies.

Recurrent Lupus nephritis in the Second Allograft of a Patient with Systemic Lupus erythematosus

Lupus glomerulonephritis is a common and serious complication of systemic lupus erythematosus (SLE) affecting up to 50% of lupus patients. Recurrent lupus nephritis is rare, complicating as low as 1% of the lupus transplant population according to some authors. However, it may be underreported with more realistic recurrent rates oscillating from 2.8 to 8.7%. We report the case of a patient with SLE who lost her first allograft 4 years after transplantation with a diagnosis of de novo fibrillary glomerulopathy. She underwent a second renal transplantation and her renal function was stable for the past 5 years. She now presented with skin rash, arthralgias and positive lupus serologies. Her creatinine was slightly elevated and proteinuria was also noted. A renal biopsy performed revealed a recurrent focal proliferative lupus nephritis (WHO III). Retrospectively, we believe that her first allograft was also lost to recurrent lupus nephritis. This is a unique case of recurrent lupus nephritis in the second allograft of a patient with SLE.

346 RENOPROTECTIVE ACTIONS OF BONE MARROW-DERIVED MESENCHYMAL STEM CELLS ARE A POTENTIAL NEW TREATMENT FOR ACUTE RENAL FAILURE.

Since acute renal failure (ARF) remains a common clinical syndrome with high mortality rates and limited treatment options, fundamentally new interventions are needed. We reported recently (Am J Physiol and Kidney Int 2005) that the infusion of mesenchymal stem cells (MSCs) is strikingly renoprotective in rats with severe ischemic ARF. Because essentially no transdifferentiation of small numbers of MSCs in the kidney was detected, we investigated alternative renoprotective mechanisms. We found striking down-regulation of proinflammatory TNF-α, IL-1β, and IFN-γ, and up-regulation of anti-inflammatory IL-10 and antiapoptotic Bcl-2, while leukocyte infiltration was similar. MSC treatment induced tubular up-regulation of bFGF and TGF-α. Renal artery and cortical blood flows were not different in MSC vs control animals. We next tested the effect of MSC conditioned medium (MSC-CM) on endothelial cells (ECs). MSC-CM acted mitogenically and inhibited apoptosis, a response also observed in tubular cells. Because growth factor (GF) expression by MSCs (express VEGF, HGF, and IGF-I, all act renoprotectively in ARF) is another potential mediator of renoprotection and since pO2 in the ischemic kidney is low, we found that VEGF expression in MSCs cultured at 5% pO2 was markedly upregulated. Our data show that the renoprotective actions of MSCs in ARF are mediated primarily through paracrine mechanisms. These elicit powerful anti-inflammatory, antiapoptotic, and mitogenic responses in renal cells that together result from the intrarenal delivery of GFs by MSCs and from their induction in the kidney of additional protective growth factors. In conclusion, we posit that our data provide the basis for the development of an MSC-based therapy for clinical ARF.