77 year old male with DM type 2, worsening creatinine and proteinuria

77-year-old white man with a history of uncontrolled type 2 diabetes mellitus, with an elevated hemoglobin A1c (10.1%) , HTN presents to clinic for evaluation of worsening renal function and proteinuria

History of presenting
Past Medical/Social history
Past surgical history
Family history
Current Medication

77-year-old white man with a history of uncontrolled type 2 diabetes mellitus, with an elevated hemoglobin A1c (10.1%) , HTN presents to clinic for evaluation of worsening renal function and proteinuria. His creat was 0.9 mg/dL 1 year ago and 1.7 mg/dL 6 months ago. His urine albumin-to-creatinine ratio 3 months ago was 0.3 g/g. During this visit, now the creatinine is 2.6 mg/dL, and he has proteinuria of 5 g/24 h. Cholesterol is within normal range , and serum albumin is slightly low at 3.3 g/dL. UA show some red blood cell casts
he has been his eye doctor regularly and Avastin injections for diabetic eye disease- He had experienced progressively blurry vision and was seen by an ophthalmologist, who prescribed intravitreal vascular endothelial growth factor (VEGF) inhibitor therapy a year ago. He was receiving intravitreal injections of bevacizumab (Avastin) (1.25 mg) in both eyes every 2 months,

Blood pressure was 119/70 mmHg, there was no clinical sign of other organ involvement. labs showed thrombocytopenia (67G/L) and mechanical hemolytic anemia: hemoglobin = 6.9 g/dL, reticulocyte = 195G/L, presence of schistocytes, Lactate Dehydrogenase (LDH) = 1258 UI/L and haptoglobin < 0.7 g/L. Extensive laboratory investigations were performed for the differential diagnosis of cytopenias. Antinuclear factors were negative, as were antibodies for antiphospholipid syndrome and scleroderma. ADAMTS 13 activity was 79%, complement investigations were normal (C4, C4, CH50, Factor I and H, anti-Factor H antibody).

DM
HTN
DYSLIPIDEMIA
DM retinopathy

DM

glipizide,
metformin,
lisinopril,
amlodipine
Avastin eye injections

positive for icterus, no diarrhea, no gross hematuria, no abdominal pain

General

Normocephalic, conjunctivae/corneas clear. PERRL, EOM's intact.Septum midline. Mucosa normal. No drainage or sinus tenderness.

Heent

no thyromegaly, conjunctiva normal , normal dentition, no JVD

Neck

no carotid bruits, trachea midline, no lymphadenopathy,

Cardiovascular

RRR, no murmur or extra heart sounds auscultated.

Lungs

CTAB, no respiratory distress or retractions. No wheezing.

Abdomen

Soft, Non tender on palpation , normal BS, no hepatosplenomegaly. No rebound

Extremities

extremities normal, atraumatic, no cyanosis or edema, pulses positive and symmetric

Skin

normal turgor, no rashes,

Neurological Exam

no focal neurological deficits, normal power, sensations normal. reflex within normal range

Bio Chemistry
Pathology
Microbiology
Hematology
Miscellaneous

Sodium: WNL meq/L( normal 135-145 meq/L)

Potassium: WNL meq/L (normal 3.5-5.0 meq/L)

Chloride: WNL meq/L(normal 96-108 meq/L)

Bicarb: WNL meq/L(normal 22-30 meq/L)

Magnesium: WNL mg/dl ( normal 1.7 to 2.2 mg/dL )

Phos.: WNL mg/dl ( normal 2.8 to 4.5 mg/dL)

Bun: 55 mg/dl ( normal 6-23 mg/dL)

Creat: 2.6 mg/dl ( normal 0.7 -1.3 mg/dL)

Liver Enzymes - SGOT/AST: WNL U/L ( normal 1-35 )

SGPT/ ALT: WNL U/L ( normal 1-45 )

GGT: WNL U/L ( normal 8-38 )

Direct Bilirubin: 0.8 mg/dl ( normal 0.1-0.3 )

Total Bilirubin: 1.7 mg/dl ( normal 0.1 - 1.2 )

The mesangial areas showed diffuse and focal nodular expansion by matrix material with segmental mesangiolysis. The arteries displayed moderate intimal fibrosis, and the arterioles showed prominent afferent and efferent hyalinization. Immunofluorescence was negative for significant glomerular immune complex deposition. . Twenty-six glomeruli were observed, of which 11 were ischemic with fibrin thrombi within glomerular capillary loops. Thrombi were present in interlobular arteries, arterioles and glomerular capillaries with fibrinoid deposit. No duplication of the glomerular basement membranes was found. the pathologic findings showed renal TMA in a background of diabetic nephropathy.

not applicable

Hemoglobin: 6.9 g/dl ( normal 13.9 -16.3)

Hematocrit: 23 % ( normal 42-52 % )

White Count: WNL ( normal 4,500 to 11,000 WBCs per microliter)

Platelets: 67 ( normal 150,000 to 450,000 platelets per microliter)

Differential: WNL

not applicable

Suggested case questions to create interactive quiz. please create questions choices with explanations

1. what is the differntial diagnosis of this case ? ( atleast 4 recommended ) . give alteast 4 plausible choices with one right answer and explanation for each choice.
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B.
C.
D,

2. What is the next step that will help in diagnosis of this case ? give alteast 4 plausible choices with right answer and explanation for each choice.
A.
B.
C.
D.

3. What are the management and therapeutic options for this case ? give alteast 4 plausible choices with right answer and explanation for each choice.
A.
B.
C.
D.

CORRECT ANSWER IS B

1.Progression to nephrotic syndrome at such a rapid pace is not typical of chronic diabetic nephropathy.

2. Avastin – Bevacizumab is a human monoclonal antibody against VEGF. It is known to cause is known to cause damage to endothelial cells that can lead to a pattern resembling acute thrombotic microangiopathy. The von Willebrand factor-cleaving protease (ADAMTS13) was 120% of reference range activity, ruling out any ADAMTS13 deficiency and thrombotic thrombocytopenic purpura. No diarrhea was noted, which suggests that there was no typical hemolytic uremic syndrome.

3.Renal vein thrombosis (RVT) describes a condition in which thrombus forms in the renal veins or their branches. – It should be suspected in patients with nephrotic syndrome who present with new onset of flank pain or generalized abdominal pain, new onset of gross hematuria, or unexplained AKI. Bilateral acute RVT can present with acute kidney injury (AKI) and typically presents with symptoms of renal infarction, including flank pain, microscopic or gross hematuria, a marked elevation in serum lactate dehydrogenase (without change in transaminases). chronic RVT most often has an insidious onset and produces no symptoms referable to the kidney.

4.Cryoglobulinemia is defined as the persistent presence in serum of abnormal immunoglobulins (Igs) that precipitate at low temperatures and dissolve again upon warming. In type I cryoglobulinemia, the cryoglobins are monoclonal antibodies typically IgG or IgM or free Ig light chains which develop in setting of protein-secreting monoclonal gammopathies. On light and immunofluorescence microscopy, membranoproliferative pattern of injury of glomerulonephritis is most commonly observed (in 60 to 80 percent), with endocapillary proliferation and subendothelial and/or intraluminal deposits of cryoglobulins, Igs, and/or complement proteins. Patients have nephritic/nephrotic syndrome with various levels of kidney dysfunction. Abnormal serologic studies include low C4 in three-quarters and low C3 in half. Less commonly seen, mesangial proliferative glomerulonephropathy, intraglomerular hyaline thrombi, and vasculitis with fibrinoid necrosis are seen. Eosinophilic refractile intracapillary “cryo-plugs” that are strongly periodic acid–Schiff (PAS) positive are due to the IgM component of these deposits. In this Patient Immunofluorescence was negative and also complement studies are normal.

REFERENCE

Bevacizumab-associated glomerular microangiopathy – PubMed (nih.gov)

A severe case of bevacizumab-induced thrombotic microangiopathy – PubMed (nih.gov)

77 year old male with DM type 2, worsening creatinine and proteinuria

By: Medcase Editor