Minimal change disease associated with anti-PD1 immunotherapy: a case report.

BACKGROUND: Oncologic immunotherapy is a form of therapy intended to reactivate the immune response to tumor cells using agents that modulate immune checkpoints, such as programmed cell death protein 1 and its ligand (PD-1/PD-L), and cytotoxic T-lymphocyte-associated antigen 4. Along with activation of the immune system to tumors, immune-mediated kidney side effects have been reported, most of which are cases of interstitial nephritis. Glomerular disease, however, appears rare. CASE PRESENTATION: Herein, we describe a patient with nephrotic syndrome related to treatment with an anti-PD1 antibody for Hodgkin lymphoma. Following the third dose of anti-PD1 antibody, the patient developed massive proteinuria and nephrotic syndrome. Kidney biopsy showed diffuse podocyte foot process effacement upon electron microscopy, which was consistent with minimal change disease. Corticosteroid treatment yielded full and rapid remission of nephrotic syndrome in 1 month. CONCLUSION: The present case suggests an association between anti-PD1 therapeutic immune activation and the development of nephrotic syndrome. Given the increasing prevalence of oncologic immunotherapy, patients should be routinely monitored for kidney side effects associated with these agents.

Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy.

Expansion microscopy (ExM), a method for improving the resolution of light microscopy by physically expanding a specimen, has not been applied to clinical tissue samples. Here we report a clinically optimized form of ExM that supports nanoscale imaging of human tissue specimens that have been fixed with formalin, embedded in paraffin, stained with hematoxylin and eosin, and/or fresh frozen. The method, which we call expansion pathology (ExPath), converts clinical samples into an ExM-compatible state, then applies an ExM protocol with protein anchoring and mechanical homogenization steps optimized for clinical samples. ExPath enables ∼70-nm-resolution imaging of diverse biomolecules in intact tissues using conventional diffraction-limited microscopes and standard antibody and fluorescent DNA in situ hybridization reagents. We use ExPath for optical diagnosis of kidney minimal-change disease, a process that previously required electron microscopy, and we demonstrate high-fidelity computational discrimination between early breast neoplastic lesions for which pathologists often disagree in classification. ExPath may enable the routine use of nanoscale imaging in pathology and clinical research.

Quantitative analysis of four types of primary glomeropathy by application of a decision forest to ultrasonic and laboratory characteristics.

The aim of this study was to apply a decision forest to analysis of the ultrasound characteristics and laboratory test indices of four types of primary glomerulopathy, and quantitative analysis of the four pathologic types using a combination of these two methods. The decision trees were derived from 41 clinical indices and 5 characteristic sonographic indices obtained for the left kidney. Fifty-six patients who had undergone ultrasound-guided renal biopsy were reviewed retrospectively, and on pathologic examination, the patients were diagnosed with primary glomerulopathy, which includes mesangial proliferative glomerulonephritis, membranous nephropathy, immunoglobulin A nephropathy and minimal change disease. In this study, eight characteristic indicators were correlated with pathologic type in the 56 cases of primary glomerulopathy. The order calculated by decision forests, from high to low, is proteinuria, length of kidney, serum creatinine, plasma albumin, area of kidney, total protein, thickness of renal parenchyma, 24-h urine protein. The glomerulopathy with the highest ++++ proteinuria is membranous nephropathy, which accounts for 39.2% (22/56) of the total sample; this was followed by minimal change disease, mesangial proliferative glomerulonephritis and immunoglobulin A nephropathy. On the basis of our analysis of 41 clinical indices, the key indices for quantitative analysis of primary glomerulonephritis are laboratory tests, and these include urine protein, serum creatinine, plasma albumin, total serum protein and 24-h urine protein. The three key sonographic features are measurement indices: renal length, renal area and renal parenchymal thickness. From the eight characteristic indicators, we observed that with respect to severity (from most severe to least severe), the four types of glomerulopathy are membranous nephropathy, minimal change disease, mesangial proliferative glomerulonephritis and immunoglobulin A nephropathy.

Serial Tc-99m MAG3 renography evaluating the recovery of acute kidney injury associated with minimal change nephrotic syndrome.

Acute kidney injury (AKI) is a well-recognized complication of minimal change nephrotic syndrome (MCNS). Previous reports support the concept that AKI associated with MCNS is reversible; however, information regarding the hemodynamic basis of AKI in MCNS is insufficient. We herein describe a case of AKI in a man with MCNS. In this case, monitoring the longitudinal changes in renal perfusion using serial Tc-99m-MAG3 renal scanning was beneficial for evaluating the pathophysiological background associated with the development of AKI. The potential impact of serial renal scanning in MCNS patients with AKI will also be discussed.

[Family occurrence of steroid-sensitive idiopathic nephrotic syndrome]. / Familiaer forekomst af steroidsensitivt idiopatisk nefrotisk syndrom.

Nephrotic syndrome (NS) presented within three weeks in siblings aged six and ten years. Both children experienced proteinuria, hypoalbuminaemia and oedema, with the most pronounced symptoms in the older. Standard treatment with prednisolone led to remission of the nephrotic syndrome in the younger, whereas the older required additional therapy with tacrolismus before remission. In view of the low incidence of NS in children, a near simultaneously onset in two siblings must lead to genetic elucidation. Genetic disorders and other causes of childhood NS are discussed.

Prediction of tubulo-interstitial injury by Doppler ultrasound in glomerular diseases: value of resistive and atrophic indices.

BACKGROUND: Doppler ultrasound is increasingly used in Nephrology for diagnosis of renovascular hypertension and evaluation of allograft dysfunction. However, its utility in glomerular disease remains controversial. OBJECTIVES: Using Doppler Ultrasound, we prospectively tested the role of resistive and atrophic indices in predicting tubulointerstitial lesions in patients with glomerular disease as demonstrated by renal biopsy. METHODS: Seventy one patients with primary or secondary glomerular diseases were examined by Doppler ultrasonography immediately before renalbiopsy. The resistive and atrophic indices (RI & AI) were calculated and compared with histologic changes in biopsy specimen. RESULTS: Receiver Operator Characteristics analysis showed RI of 0.60 as an optimal value for discriminating tubulointerstitial changes with sensitivity of 82.7% and specificity of 92%. An AI of 0.65 was shown to be optimal for discriminating tubulointerstitial injury with sensitivity of 69.2% and specificity of 85%. The combination of the two indices had not been found to be superior to either index alone. There was a significant correlation between atrophic and resistive indices. (r=0.358, p< 0.01). It was observed that older age, smoking, elevated AI and RI, low GFR, high serum cholesterol and Hypertension were found to be significantly associated with the presence of tubulointerstitial injury in the univariate analysis whereas only elevated AI and RI were found to predict tubulointerstitial injury in multivariate analysis. CONCLUSION: Measurement of RI by Doppler ultrasound can be considered as a supplementary diagnostic tool in glomerular diseases to predict the severity of tubulointerstitial injury.

Minimally dilated obstructive nephropathy initially suspected as pre-renal azotemia in a kidney donor with volume depletion.

Although ultrasonography is regarded as the gold standard in the diagnosis of obstructive nephropathy, dilatation is sometimes not observed by ultrasonography. We report upon a case of minimally dilated obstructive nephropathy due to an ureter stone in a kidney donor with volume depletion. A 54-year-old man was admitted due to anuria and abdominal pain of 2 days duration. Ten years previously, his right kidney was donated for transplantation, and one month before admission, he abstained from all food except water and salt, for 30 days for religious reasons. He had lost 8 kg of body weight. On admission, he had clinical signs of volume depletion, i.e., a dehydrated tongue and decreased skin turgor. Laboratory data confirmed severe renal failure, his blood urea nitrogen level was 107.3 mg/dL, and his serum creatinine 16.5 mg/dL. The plain X-ray was unremarkable and ultrasonography showed only minimal dilatation of the renal collecting system. On follow-up ultrasonography, performed on the 5th hospital day, the dilatation of the collecting system had slightly progressed and a small stone was found at ureter orifice by cystoscopy. Removal of stone initiated dramatic diuresis with a rapid return of renal function to normal by the third day.

Pulmonary thrombosis in a 10-year-old child with minimal change disease and nephrotic syndrome. A clinical, radiologic, and pathologic correlation with literature review.

The nephrotic syndrome has long been recognized as a hypercoagulable state. Arterial thrombosis is a rare complication of the syndrome. Diuretics and steroids, standard treatment for exacerbations, have been implicated as contributing to the development of arterial thrombosis. The authors present the pathologic, clinical, and radiologic findings of a patient with nephrotic syndrome and minimal change disease. The patient died of pulmonary thrombosis while on high-dose steroid therapy for an acute exacerbation of proteinuria following a recent hospital admission for chest pain and dyspnea.

Arterial thrombosis: a rare complication of the nephrotic syndrome.

Arterial thrombosis is a rare complication of the nephrotic syndrome, occurring mainly in men. Two cases of arterial thrombosis are described, the first affecting a 54-year-old man in whom aortic thrombosis initiated the nephrotic syndrome and who relapsed 1 year later resulting in graft thrombosis, the second affecting a 15-year-old male patient with extensive popliteal and distal arterial thrombosis, followed by recurrent venous bypass thrombosis. A review of the literature shows that arterial thrombosis occurs primarily in the femoropopliteal, renal and coronary arteries. The genesis of arterial thrombosis in patients with nephrotic syndrome involves increased blood viscosity, platelet adhesion and aggregation, high levels of fibrinogen, low levels of serum antithrombin III, diuretic agents and steroid therapy. For high-risk patients with low levels of plasma albumin or those receiving steroids, anticoagulation therapy should be introduced to prevent thrombosis. Urine protein should be evaluated in patients with arterial thrombosis of unknown origin.

[Improvement in nuclear medicine diagnosis of kidney function using 99m technetium mercaptoacetyltriglycine (MAG3)]. / Verbesserung der nuklearmedizinischen Nierenfunktionsdiagnostik durch den Einsatz von 99m-Technetiummercaptoacetyltriglycin (MAG3).

Renal scintigraphy and clearance measurement are indispensable in nephro-urologic disorders. A continuous series of 103 sequential scintigraphies and clearance measurements were performed with the new technetium-labelled agent MAG3 (Gamma-kamera, Phillips Tomo Diagnost) and 131I-orthohippuric acid (OIH) using the Oberhausen method (Nucleopan, Siemens). The time-activity curves obtained with the two radionuclides agreed exactly. Reaching a tubular excretion rate of nearly 90%, the clearance of MAG3 differed by no more than 6% from the OIH clearance in 95% of the cases. The factor between clearances of the two radionuclides was determined by means of a commercially available software according to the Oberhausen method and amounted to 0.59 +/- 0.09. The favorable physical properties and high activity of MAG3 permit exact examination of tubular function and better assessment of renal morphology than hippuran-labelled radionuclides. The low radiation dose combined with a better spatial resolution, especially, the constant availability in a nuclear medicine department should give the preference to MAG3.

Gallium 67 scintigraphy in glomerular disease.

To evaluate the diagnostic usefulness of gallium 67 scintigraphy in glomerular disease, 45 patients with various glomerulopathies, excluding lupus nephritis and renal vasculitis, were studied. Persistent renal visualization 48 hours after the gallium injection, a positive scintigram, was graded as + (less than), ++ (equal to), and +++ (greater than) the hepatic uptake. Positive scintigrams were seen in ten of 16 cases of focal segmental glomerulosclerosis, six of 11 cases of proliferative glomerulonephritis, and one case of minimal change, and one of two cases of membranous nephropathy; also in three of six cases of sickle glomerulopathy, two cases of diabetic neuropathy, one of two cases of amyloidosis, and one case of mild chronic allograft rejection. The 25 patients with positive scans were younger than the 20 with negative scans (31 +/- 12 v 42 +/- 17 years; P less than 0.01), and exhibited greater proteinuria (8.19 +/- 7.96 v 2.9 +/- 2.3 S/d; P less than 0.01) and lower serum creatinine values (2 +/- 2 v 4.1 +/- 2.8 mg/dL; P less than 0.01). The amount of proteinuria correlated directly with the intensity grade of the gallium image (P less than 0.02), but there was no correlation between the biopsy diagnosis and the outcome of the gallium scan. It was concluded that gallium scintigraphy is not useful in the differential diagnosis of the glomerular diseases under discussion. Younger patients with good renal function and heavy proteinuria are likely to have a positive renal scintigram regardless of the underlying glomerulopathy.

Nephrotic syndrome in two patients with cured Hodgkin's disease.

Two cases of lipoid nephrosis (minimal change glomerulonephritis) in patients cured of Hodgkin's disease are reported and the literature is reviewed. Cases reported to date have shown a close temporal relationship between this renal lesion and the presence of Hodgkin's disease. The patients reported are 11 and 9 years without evidence of active malignancy after successful treatment for Hodgkin's disease. Each had abnormal immunologic parameters, depressed T4 (helper) cells and increased T8 (suppressor) cells, which may predispose to the development of the nephrotic syndrome. However, the advent of this complication is not necessarily a harbinger of recurrent lymphoma.

Congenital lipoid nephrosis with left renal vein thrombosis and Chiari's syndrome.

An infant with primary congenital lipoid nephrosis then developed left renal vein thrombosis and secondary hepatic vein obstruction. This was shown by inferior venacavography. The thrombus detached subsequently, and the child died from massive pulmonary embolism.