A 53-year-old man with long-standing hypertension and poor adherence to therapy attended the emergency department for hypertensive crisis (BP 244/144 mmHg). Examination revealed bimalleolar edema. Laboratory tests showed anemia in transfusion range (Hb 6.9 mg/dl) with no evidence of hemolysis (smear without schistocytes, LDH 228 IU/L, reticulocytes 0.79%, haptoglobin 2.8 mg/dl; with normal coagulation, platelets 219,000 mcL). We observed significant deterioration of renal function (Cr 3.8 mg/dl) with subnephrotic proteinuria (protein/creatinine ratio 0.82), without hematuria; the sediment was irrelevant. Reviewing previous studies, without data from 7 years earlier, we found that at the time the patient had normal renal function, without urinary alterations. We performed a study of secondary hypertension, with negative or normal results. In addition, we requested a glomerular protocol with negative antinuclear antibodies (ANA), anti-neutrophil cytoplasm antibodies (ANCA), cryoglobulins and phospholipase A2 receptor antibodies (anti-PLA2R). Immunoglobulins with IgM were 38 IU/ml; the rest, within normal range. There was no monoclonal peak (serum kapppa/lambda ratio 1.17) and complement C3 and C4 were also normal. Proteinogram without alterations. Serology (HCV, HBV, HIV, syphilis), fecal occult blood and tumor markers were also negative. We performed a renal biopsy and obtained the diagnosis of CKD in the context of malignant/accelerated HTN. During admission, we detected a new palpable inguinal adenopathy, so we requested a CT scan, which revealed hepatosplenomegaly and supra- and infradiaphragmatic subcentimetric adenopathies, striking in number, and with uptake in PET-CT, all suggestive of chronic lymphoproliferative syndrome. The biopsy of the inguinal adenopathy described changes compatible with hypervascular Castleman's disease, HHV8 and EBV negative.

We began treatment with cortisone at a dose of 1 mg/kg per day and siltuximab. The evolution was torpid, with the development of pancytopenia and worsening of renal function (Cr 5.6 mg/dl) with an increase in proteinuria to nephrotic range (6.5 protein/creatinine ratio), clinical and analytical nephrotic syndrome. Other associated alterations included severe hypothyroidism and polyclonal hypergammaglobulinemia, not previously present. In this context, acute respiratory failure and decreased level of consciousness occurred, requiring transfer to the ICU, where death finally occurred due to cardiac complications (arrhythmia complications) 2 months after the onset of the hematologic disease.

A 66-year-old male, who came to the emergency department for asthenia, weight loss and progressive dyspnea of several weeks of evolution. On some occasions, low transient fever. Chest X-ray showed a rounded nodular image in the upper lobe of the right lung. The study continued with CT and confirmed the presence of a well-demarcated right subpleural nodule of 9 × 7 mm, without metabolic activity in PET-CT. In addition, the study described supra- and infradiaphragmatic adenopathies (laterocervical mediastinal, axillary, retroperitoneal periaortic and interaortocaval and bilateral inguinal, the larger ones reaching 12 mm). No organomegaly. During admission, the patient developed a clinical and biochemical nephrotic syndrome (protein/Cr ratio 6.5 g) with microhematuria (sediment 3–5 red blood cells/field) and normal renal function (Cr 0.85 mg/dl). A review of the history showed that previous renal function was normal, without urinary alterations. The immunological study found IgG anticardiolipin (ACA) of 15 U/ml, positive ANCA (not studied by IFA), positive ANA at low titer (1/80), with negative anti-DNA and extractable nuclear antibodies (ENA) and complement consumption (C3 of 57 mg/dl and C4 of 10 mg/dl). In addition, there was anemia in transfusion range (Hb 7.2 mg/dl), without data of hemolysis, mild thrombocytopenia (platelets 138,000 mcL), increased ESR to 41 and polyclonal hypergammaglobulinemia (IgG 1875 mg/dl, IgM 589 mg/dl, IgA 387 mg/dl). We then performed renal biopsy, which revealed membranous nephropathy with focal endocapillary proliferation and C1q deposits, highly suggestive of secondary etiology. PLA 2R negative in biopsy, C4d positive. The analytical study continued with serology (HCV, HBV, HIV, syphilis) and negative tumor markers. Bone marrow biopsy was normal and the puncture of solitary pulmonary nodule showed no evidence of malignancy. Finally, we performed inguinal adenopathy biopsy, in which we found changes compatible with plasmocellular VHH8+ Castleman's disease (negative VHH8 in renal biopsy).

Given the underlying hematological process with renal involvement, we decided, in agreement with the internal medicine department, to initiate treatment with cortisone (prednisone 1 mg/kg per day) and rituximab (375 mg for 8 doses in total), with good clinical and analytical evolution, achieving complete remission after 3 months of treatment. Currently, 4 years after diagnosis and without immunosuppressive maintenance treatment, the patient remains asymptomatic, with preserved renal function and stable adenopathies.

A 28-year-old woman consulted for neck discomfort in the context of a painless, slow-growing left cervical mass. She also reported night sweats with no other symptoms, dry mouth, no ocular dryness, and ongoing back pain. Examination revealed milk-coffee colored skin lesions. We ordered a body CT which confirmed the presence of bilateral laterocervical adenopathies, the largest 1.5 cm and submaxillary, in the left parotid tail with metabolic activity in PET-CT. No organomegaly. We performed a biopsy of the left cervical adenopathy, showing changes compatible with hyalinovascular Castleman's disease VHH8 and negative EVB-EBER. During the follow-up by internal medicine, an occasional malar rash and ongoing joint pain in the hands and knees appeared. Suspecting a possible associated autoimmune disease (SLE or Sjögren's disease), internal medicine consulted us to extend the study. Laboratory tests showed mild anemia (Hb 10.6 mg/dl) and leukocytopenia (38,000 mcL) with mild lymphopenia. Renal function was normal, with red blood cells and protein in urine (sediment with 5–10 red blood cells/field and protein/creatinine ratio 0.38). Reviewing history, the patient had already presented similar proteinuria and hematuria at least 2 years before. The immunological study revealed positive ANA (titer 1/640) with negative anti-DNA and ENA; lupus anticoagulant positive at high titers (IgM 70, IgG 200); ACA positive (18 U/ml) and hypocomplementemia (C3 of 78 mg/dl and C4 of 6 mg/dl); normal ESR.

Due to the lab results, we started treatment with low-dose corticosteroids (prednisone 0.5 mg/kg per day), siltuximab and acetylsalicylic acid. The patient had a poor clinical and radiological evolution and required admission to the nephrology department for florid nephrotic syndrome (proteinuria up to 6 g, with hypoalbuminemia [2.8 g/dl] and generalized edema). Renal function was normal.

In this context, we started treatment with intravenous corticosteroid boluses (500 mg per 3 doses) together with oral doses at 1 mg/kg per day and scheduled a renal biopsy, with anatomopathological findings compatible with type iv lupus nephropathy and high activity index (11/24). At this point we decided to start treatment with rituximab (375 mg for 8 doses) for a joint approach to lupus nephropathy and Castleman's disease and achieved complete remission of both diseases. The patient has stable hematology lab results and is in complete renal remission. She is on maintenance treatment with prednisone (10 mg/day) and hydroxychloroquine (200 mg/day). A small flare of lupus appeared 2 years after diagnosis, with proteinuria of 1.5 g and minimal reversible deterioration of renal function (Cr 1.45 mg/dl) of probable prerenal etiology. In the sediment: microhematuria with proteinuria by ratio of 1.49. ANA positive (titer 1/320), without having been negative at any time, with negative anti-DNA and positive lupus anticoagulant (IgM 40, IgG 140). We also detected hypocomplementemia (C3 of 70 mg/dl; C4 of 6.5 mg/dl). At that time mycophenolate was associated (500 mg every 12 h), and we increased it to a dose of 1500 mg/day. From the renal point of view there was again remission of the disease (normal renal function, with persistent microhematuria and minimal proteinuria of 0.45 g). However, the systemic symptoms persisted with arthralgias and asthenia, so we agreed with the rheumatology department to associate treatment with belimumab, with good subsequent evolution after 6 months of treatment. Currently, from the nephrological point of view: residual proteinuria around 0.3−0.7 and normal renal function, without adenopathies and with improvement of the systemic symptoms. The patient continues with low-dose prednisone (5 mg/day), mycophenolate (200 mg every 12 h) and belimumab (10 mg/kg monthly), although with poor adherence.

A 45-year-old woman consulted for a slow-growing breast nodule. The imaging study showed a benign breast lesion, but, incidentally, bilateral axillary adenopathies, without lesions in other areas or organomegaly. No systemic symptomatology at that time. We performed a biopsy of one of the axillary nodes, with a diagnosis of hypervascular Castleman's disease, HHV8 and EBV negative. In the complementary study, the renal function was normal, without urinary alterations. As a result of the immunological protocol, ANA was positive at low titer (1/160), with positive anti-DNA, negative ENA and polyclonal hypergammaglobulinemia (IgG 1715 mg/dl, IgM 679 mg/dl, IgA 407 mg/dl). No complement consumption and negative ANCA, ACA and lupus anticoagulant. Bone marrow biopsy, without evidence of infiltration. In the directed interview, the patient reported chest skin lesions on some occasions, with malar rash, oral aphthous ulcers and generalized arthralgias, which she no longer presents. Treatment with hydroxychloroquine (200 mg/day) and follow-up was indicated. Two years after CD diagnosis, the patient began suffering clinical and biochemical nephrotic syndrome with proteinuria of 8 g, bimalleolar edema and hypoalbuminemia of 2.3 mg/dl and microhematuria of 5 red blood cells/field in sediment. Renal function was normal. In the immunological analysis, ANA positivity persisted, now at a titer of 1/640 with positive anti-DNA and positive anti-ENA (SS-A: ++, Ro 52: ++, SS-B: +, nucleosomes +, histones +, AMA M2: +++). She had persistent polyclonal hypergammaglobulinemia and complement consumption (C3 of 48 mg/dl and C4 of 7 mg/dl). During this time, the adenopathies remained stable. We then decided to perform a renal biopsy, that showed histology of type iv lupus nephropathy. We maintained treatment with antimalarials (hydroxychloroquine at 200 mg/day) and started treatment with intravenous corticosteroids (3 boluses of 500 mg) oral dose of 1 mg/kg per day in a descending pattern and mycophenolate (250 mg every 12 h), achieving good clinical and analytical response. Currently the patient is in complete remission, with preserved renal function and stable adenopathies. She maintains treatment with prednisone 2.5 mg every other day with mycophenolate in a descending regimen of 250 mg per day and antimalarials. The rheumatology service raised the possibility of associating belimumab before the complete withdrawal of mycophenolate.