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Background and Aims Monoclonal gammopathy of renal significance (MGRS) is a clinically and morphologically diverse kidney damage caused by monoclonal immunoglobulin (IG) produced by a "small" B-cell clone. Non-amyloid type of MGRS is considered to be rare but associated with poor kidney outcome (KO). The analysis of the prevalence, clinical and morphological spectrum and long-term renal prognosis in different degrees of hematological response (HR) in patients with non-amyloid type of MGRS became the goal of this study. Method In this one-center prospective study performed from 01.01.2011 till 01.03.2020 patients with MGRS were enrolled. Criteria of MGRS were following: i) morphologically verified monoclonal IG related kidney damage and ii) an aberrant clone in the bone marrow and/or the level of serum/urine paraprotein not met the hematological criteria for treatment initiation. Cases of renal AL-amyloidosis were excluded. The morphological spectrum of non-amyloid MGRS, treatment, hematological and renal responses (RR) were analyzed. HR was assessed depending on the type of monoclonal IG according to the accepted criteria. The presence of RR was considered as a decrease in daily proteinuria> 30% from the initial level or less than 0.5 g in the absence of a decrease in eGFR> 25% at the time of the end of follow-up. The progression of renal dysfunction was documented with a decrease in eGFR> 25% from baseline. KO was determined as initiation of renal replacement therapy or eGFR Results The prevalence of non-amyloid MGRS was 1.4% (n = 29) of all performed kidney biopsies (n = 2042). Clinical and demographic parameters of the group are presented in the figure 1. Serum or/and urine paraprotein was detected in 23 patients as κ (30.4%), IgM/κ (21.7%), IgM/λ (13.1%), IgG/κ (13.1%), λ (13.1%), IgA/κ (4.3%), IgG/λ (4.3%). Morphological spectrum of non-amyloid MGRS is shown in the figure 2. Combination of light chain deposition disease and thrombotic microangiopathy was documented in two cases. The majority of patients (82.7%) was treated with clone-specific agents. In non-IgM-associated MGRS cases bortezomib+dexamethasone (D) (n=11), melphalan+D (n=2), cyclophosphamide (CPh) +bortezomib+D (n=1), lenalidomide+D (n=1) were used. Autologous stem cell transplantation was performed in 1 case. Prednisolone+CPh based schemes were applied in 5 patients. In IgM-associated MGRS 7 patients were treated with rituximab and 1 patient with bortezomib+D due to contraindication to anti-CD20 agent. 8 patients were missed from the follow-up. HR and RR were achieved in 76.2% and 62% of the treated patients, respectively (Figure 3). The five-year cumulative renal survival was 44% in the non-amyloid MGRS group and did not significantly differ from renal AL-amyloidosis group when compared (Figure 4). Conclusion Non-amyloid type of MGRS is a clinically and morphologically diverse entity characterized by a poor renal prognosis, especially in the absence of clone-specific therapy. Treatment of MGRS should be carried out in a timely manner with the participation of a hematologist and nephrologist in order to prevent loss of kidney function and increase life expectancy.

Background and Aims The pathological patterns of myeloma-related kidney disease are various, in which myeloma cast nephropathy (MCN) and light chain deposition disease (LCDD) are two of the main patterns. Of note, in patients with multiple myeloma (MM), these two patterns of pathology can occur at the same time. However, there are limited data available showing the difference of clinical characteristics and outcomes among newly diagnosed MM patients with these three patterns of pathology. In this study, we retrospectively reviewed 42 newly diagnosed MM patients with renal biopsy-proven pure MCN, pure LCDD or MCN with coexistent LCDD in Peking University First Hospital, to describe the clinical characteristics, treatment, and outcomes, in order to help define the spectrum of prognostic profiles. Method All the native renal biopsies between September 1999 and October 2019 at Peking University First Hospital were retrospectively restudied. A total of 42 newly diagnosed MM patients with pure MCN (n=24), pure LCDD (n=8) and MCN with coexistent LCDD (n=10) were enrolled. The clinical features, as well as prognostic risk factors for renal survival and overall survival were retrospectively investigated. Results The 42 parents consisted of 26 men and 16 women with a mean age of 53.2±10.9 years. There was no significant difference in age and gender among the 3 groups. Patients with pure LCDD had significantly higher hemoglobin levels, a higher percentage of albumin in urine protein, a lower incidence of progressing to ESRD and more likely to present with AKD than patients with pure MCN or with MCN+LCDD. Patients with pure LCDD had significantly higher serum creatinine levels, a lower eGFR, a lower incidence of death and more likely to present with nephrotic syndrome than patients with pure MCN, but no different than patients with MCN+LCDD. No significant difference between pure MCN and MCN+LCDD. Median renal survival in LCDD group (not reached) was significantly higher compared to MCN (11 months, p = 0.002) group and MCN+LCDD group (1months, p = 0.012, Figure 1). Median overall survival in LCDD group (not reached) was significantly higher compared to MCN (39 months, p = 0.014) group, but had no difference with MCN+LCDD group (not reached, p = 0.199, Figure 2). According to the multivariate analysis, the independent predictors of renal survival were hemoglobin (HR: 0.957, 95% CI: 0.922-0.994; p = 0.022) and eGFR (HR: 0.940, 95% CI: 0.880-0.995; p = 0.034), the independent predictors of overall survival were hemoglobin (HR: 0.943, 95% CI: 0.895-0.993; p = 0.025) and pure MCN (HR: 7.597, 95% CI: 1.171-49.272; p = 0.034). Conclusion Patients with MCN+LCDD presented similar in clinical characteristics to patients with pure MCN and both suffer from more serious and more urgent renal damage than patients with pure LCDD. However, the overall survival in patients with MCN+LCDD was similar to patients with pure LCDD while the renal survival was worse. Hemoglobin and eGFR were independent predictors of renal survival and hemoglobin and pure MCN were independent predictors of overall survival.

Light chain deposition disease (LCDD) is characterized by the tissue deposition of monotypic immunoglobulin light chains of either kappa or lambda isotype. It is the archetypal systemic disease that is most frequently diagnosed on a kidney biopsy, although the deposits may involve several other organs. This brief review focuses on the clinicopathological features of LCDD-associated nephropathy with an emphasis on the diagnostic and therapeutic difficulties related to this elusive condition.

Immunoglobulin D (IgD) multiple myeloma (MM) is a very rare form of myeloma affecting less than 2% of all myeloma patients. It has a multiorgan involvement with renal failure being the key feature. We present here a case of IgD MM in a 62-year-old white male, smoker with past medical history of hypertension, who presented to emergency department with complaints of lower abdominal pain, constipation and decreased urination. Physical exam was unremarkable. Laboratory investigation showed S.Cr 5.99 mg/dL, hemoglobin 8.7 g/dL and corrected S.Ca 10.6 mg/dL. Urine dipstick showed 100 protein and TP/Cr ratio was 23. Serology was positive for serum free lambda chain level of 8,947.6 mg/L as well with free κ/λ ratio < 0.01. The results of serum and urine electrophoresis and immunofixation were also supportive of diagnosis of IgD MM. IgD level was remarkably elevated (27,300 mg/L) too. CT scan of abdomen/pelvis was negative for obstructive uropathy. Skeletal survey showed a solitary lytic lesion in the iliac crest. His kidney function deteriorated next day requiring hemodialysis. The bone marrow biopsy was positive for plasma cell hypercellularity (70-80%) and flow cytometry showed 8% monoclonal IgD lambda plasma cells. The patient was started on bortezomib and dexamethasone and he underwent bone marrow transplant 6 months later. He is doing well hematologically now but he remains dialysis-dependent. IgD MM is a very rare disease affecting younger population with poor prognosis; patients often end up on hemodialysis despite better control of the hematological component.

A 19 month old boy with AIDS developed clinically unex-plainable proteinuria. Biopsied renal tissue was examined by light microscopy, transmission electron microscopy, and immunofluorescence. Findings included an increase of mesangial matrix with occasional nodular sclerosis, mesan-gial hypercellularity, and glomerular deposits of kappa and lambda light chains. There were deposits of kappa, but not lambda, light chains in the arteriolar walls, and around the tubular and interstitial capillary basement membranes. Quantitative urinary Immunoelectrophoresis revealed an extremely high urinary concentration of kappa light chain. These changes are diagnostic of light chain nephropathy. The rarity of light chain nephropathy in childhood and its occurrence in a patient with AIDS make this case unusual.

Es wird der Fall eines 47-jahrigen Patienten geschildert, der nach mehreren mit Antibiotika zur Ausheilung gebrachten Prostatitiden mit einer akuten Prostatitis mit Serumkreatininerhohung und Makrohamaturie in unserer nephrologischen Ambulanz vorstellig wurde. Der Patient war leistungsfahig und belastbar und berichtete uber keine Medikamenteneinnahme auser der verordneten Antibiotikamedikation. Die initialen Kernbefunde klassisches nephritisches Sediment, relevante Proteinurie sowie beginnendes akutes Nierenversagen lenkten den Verdacht auf eine Glomerulonephritis, der sich jedoch im Befund der Biopsie nicht bestatigte. Erst anhand einer Knochenmarkbiopsie und durch Nachbefundung der Nierenbiopsie war eine Diagnosestellung – isoliert vaskulare Leichtkettennephropathie sowie plasmazellular differenziertes Marginalzonen-B-Zell-Lymphom – moglich. Deren Ursachen blieben teilweise unklar. Nach initialer Antibiotika- und Steroidbehandlung wurde der Patient onkologisch weiterbetreut und nach dem R-CHOP-Schema (Rituximab, Cyclophsophamid, Vincritstin, Daunorubicin, Prednisolon) behandelt.

1. What is (are) this patient’s most striking laboratory result(s)? 2. How do you explain this patient’s most striking laboratory result(s)? 3. What condition(s) does this patient’s laboratory and other findings suggest? 4. Which laboratory and non-laboratory test(s) are appropriate to order on this patient and why? 5. What is this patient’s most likely diagnosis? 6. What is the pathophysiology of this patient’s condition(s)? 7. What are the principal complications, their cause(s), and the prognosis in individuals with this patient’s condition? 8. What is the most appropriate treatment for this patient’s condition?

Two patients with light chain nephropathy are described. The diagnosis and management of this rare condition is discussed.

Article, 信州医学雑誌 29(2): 216-224(1981)

In Reply. —Craig and Powell have provided convincing evidence that patients with multiple myeloma and light chain proteinuria are at risk for renal insufficiency from NSAID, most likely on the basis of overt or occult light chain nephropathy. Prostaglandins are involved in the compensatory response to renal injury or reduced renal mass from many causes, as we have recently discussed elsewhere. 1 As noted by Craig and Powell, and illustrated by their case report, the risk in patients with myeloma is usually multifactorial (on the basis of advanced age, other medications, and so on). Whether or not all patients with multiple myeloma are at risk for renal insufficiency from NSAID is open to question. The experience with systemic lupus erythematosus, a systemic disease with renal involvement in