Ultrastructural identification of a proximal tubulopathy without crystals in a relapsed multiple myeloma patient.

A multiple myeloma patient, who had been treated with a hematopoietic stem cell transplant, underwent a renal biopsy for investigation of a possible relapse of disease as indicated by increased serum creatinine and positive urinary Bence-Jones protein containing increased kappa light chain. Paraprotein-related renal disease was not evident by light microscopy or immunofluorescence microscopy however electron microscopy demonstrated a proximal tubulopathy with intracytoplasmic non-crystalline inclusions. The ultrastructural findings suggested possible end-organ involvement by the disease and follow-up studies subsequently revealed a relapsed multiple myeloma in the patient. The case exemplifies the usefulness of electron microscopy in detecting paraproteins that, in some instances, may be difficult to demonstrate by other techniques.

An unusual pattern of peritubular capillary injury involving apoptosis in a renal transplant patient.

Microvascular injury is an important factor in renal allograft survival. Repeated episodes of endothelial injury from chronic antibody-mediated rejection typically manifest at the ultrastructural level as circumferential multilayering of remodeled glomerular basement membrane material and peritubular capillary basal lamina. In contrast to this typical pattern of microvascular injury, a renal transplantation case is presented in which focally dilated and multilayered segments of peritubular capillary basal lamina bearing lipid droplets were interspersed with ultrastructurally normal unilayered segments of basal lamina devoid of lipid droplets. Glomerular basement membranes were not affected by this process. The peak incidence of lipid droplets within the peritubular capillary walls coincided with a peak in apoptotic activity within the allograft. Lesser amounts of the same lipidic material were identified in the mesangial matrix and an arteriolar wall. Mesangial electron-dense deposits were detected at two weeks posttransplantation and their appearance coincided with elevated immunological activity in the glomeruli, as determined by immunofluorescence microscopy. The unusual ultrastructure and immunological activity observed in this case may reflect a process of impaired apoptotic clearance within the allograft. The six biopsies from a single patient are discussed in the setting of a highly sensitized renal transplant recipient who received prophylactic terminal complement blockade by eculizumab. The findings may be relevant to the study of apoptosis, efferocytosis, microvascular injury, eculizumab, rejection, lupus, and drug-related disease.

Structure and Function of the Kidney in Septic Shock. A Prospective Controlled Experimental Study.

RATIONALE: It is unclear how septic shock causes acute kidney injury (AKI) and whether this is associated with histological change. OBJECTIVES: We aimed to determine the nature and extent of changes in renal structure and function over time in an ovine model of septic shock. METHODS: Fifteen sheep were instrumented with a renal artery flow probe and renal vein cannula. Ten were given intravenous Escherichia coli to induce septic shock, and five acted as controls. Animals were mechanically ventilated for 48 hours, while receiving protocol-guided parenteral fluids and a norepinephrine infusion to maintain mean arterial pressure. Renal biopsies were taken every 24 hours or whenever animals were oliguric for 2 hours. A renal pathologist, blinded to tissue source, systematically quantified histological appearance by light and electron microscopy for 31 prespecified structural changes. MEASUREMENTS AND MAIN RESULTS: Sheep given E. coli developed septic shock, oliguria, increased serum creatinine, and reduced creatinine clearance (AKI), but there were no changes over time in renal blood flow between groups (P > 0.30) or over time within groups (P > 0.50). Renal oxygen consumption increased only in nonseptic animals (P = 0.01), but there was no between-group difference in renal lactate flux (P > 0.50). There was little structural disturbance in all biopsies and, although some cellular appearances changed over time, the only difference between septic and nonseptic animals was mesangial expansion on electron microscopy. CONCLUSIONS: In an intensive care-supported model of gram-negative septic shock, early AKI was not associated with changes in renal blood flow, oxygen delivery, or histological appearance. Other mechanisms must contribute to septic AKI.

Electron-dense deposit in renal transplant patients on eculizumab may be drug-derived.

Eculizumab is a monoclonal antibody that inhibits the conversion of complement protein C5 to C5a and C5b. Eculizumab has been used to treat some disorders of complement regulation owing to its ability to inhibit terminal complement activation. The efficacy of eculizumab in reducing complement-mediated microvascular injury in renal allografts is currently the subject of trials. Electron-dense deposit was detected in allograft biopsies from three highly sensitized recipients of renal transplants, all of whom had received prophylactic eculizumab therapy. In two cases, the deposit was probably drug-derived whilst in the third case the deposit was probably derived from recurrent disease. The cases demonstrate the potential difficulty in interpreting electron-dense deposit in renal allograft biopsies, particularly in the setting of eculizumab therapy.

Ultrastructural observations in a case of BK virus nephropathy with viruses in glomerular subepithelial humps.

BK virus nephropathy is a known cause of renal transplant dysfunction and failure. The disease is identified by examination of kidney biopsy tissue utilizing histopathological techniques. Ultrastructural examination of two glomeruli revealed pathology within one glomerulus. Glomerular basement membranes contained subepithelial humps of deposit-like material and BK viruses were identified within this material. Viruses were identified within intertubular capillaries. There was evidence of cytoplasmic clearance of viruses from the glomerular basement membrane by podocytes. The findings may be relevant to the investigation of hump formation and antigen clearance in BK virus nephropathy and postinfectious glomerulonephritis.