Chronic Glomerulonephritis with immune complexes
Short Summary

42-year-old female with chronic renal insufficiency secondary to immune complex mediated glomerulonephropathy, hypertension, Type 2 diabetes mellitus, and hyperlipidemia. The recommended solution for her is kidney transplant.

Patient's Questions
1)    Any further diagnostic tests that could lead to better treatment ?

2)    Any suggestion for conservative therapy

3)    Is it time for kidney transplant or is it better to wait until there is further renal deterioration?
Her main question is whether to try to go for an immediate kidney transplant or wait for further deterioration in renal function.
 
Medical Background

 
Patient's History
Diagnosis:
Chronic Glomerulonephritis with immune complexes (per biopsy 1/2009)
Chronic Renal failure
Diabetes type II – No Target Organ Disease
Obesity (BMI>30)
Gastric Band
Hypercholesterolemia
Cholelithiasis
Blood type O+
 
Regular Medications:
VASODIP 5mg/day
ALLORIL 100mg/day
INSULIN LANTUS SOLOSTAR
INSULIN NOVORAPID FLEX PEN
VENOFER 100mg/day
VITAMIN D
 
The patient is 42 years old women, a mother of 4 children , with the above diagnosis’s list.
On March these tests results these were some of the tests results:
Creatinine: 2.2 mg/dl,  Urea: 127 mg/dl, Hb: 9.1 gr%, Na+ 139 mmol/l, K+ 3.78 mmol/l
Which show an improvement in relation to earlier results as described below.
 
·         Feb 2009
On a nephrology consultation:
The patient has chronic renal failure as of 2007. Lab results on February 2009 are :
Urea 197 mg/dl , Creatinine 3 mg/dl, Phosphorus 4.47 mg/dl, Alb 3.84 g/dl, K+ 3.34 mmol/l
Na+ 135 mmol/l , Hb 8.5 gr% ,  CCT/MDRD 18ml/min.
Decreased appetite, morning sickness, probably due to high urea.
Recommended an early preemptive kidney transplant.
 
·         Feb 2009
A summary of an ambulatory in the nephrology clinic:
Physical examination : Normal , weight 88.5 Kg, height 171 cm, normal BP, no signs of over hydration.
Support with I.V. iron supplements and erythropoietin 4000U twice a week.
Since PTH levels were increased, and since 1 alpha Vitamin D 3 have caused hypercalcemia , it was recommended to start with Mimpara 30mg once a day , while monitoring calcium and phosphorus levels. Since creatinine clearance is calculated according to MDRD-  15.9ml/minute, and since the patient also has diabetes it was recommended that the optimal solution for the patient is kidney transplant.
Meanwhile it was recommended to :
Continue with diet: protein 0.8 gr/kg of body weight, salt – 5 gr per day.
Continue with BP treatment
Start Mimpara as stated above
 
·         Pathology report  Summary– January 2009
Material : Kidney Needle Biopsy
Microscopy:
HE slides and paraffin blocks were received.
Suboptimal fixation.
Up to 18 glomeruli were seen, 5 of them with global sclerosis, 13 with open capillaries, some with thickening of Bowman, some with mesenchial sclerosis (difficult to estimate the amount of cells or levels of sclerosis because of tissue quality). Large areas of tubular atrophy and interstitial fibrosis (50% of area). In arteries slight thickening of atherosclerosis was seen.
Immunofluorescence – pseudoliniar peripheral sedimentation of IGA and C3, without sedimentation of C4,IGM,IGG,Fibrinogen. No testing was preformed to the light chaines. K,L, staining from the paraffin cuts was not successful.
EM -    (3 glomeruli in the thick cuts) - many areas of large  electron opaque sediments at the subepithelial side of the GBM, with enlargement of the GBM between and around the sediments (not in all capillaries). A focus with suspected fibrillar structures at the sediments was seen, but at high magnification , in a repeated shot – no firillar structures were seen.
The findings are of Chronic Glomerulonephritis with Immune –Complexes
As a result of suboptimal tissue in the paraffin block, immunoperoxidase tests could not be done and details of glomeruli were not seen clearly. In addition, a repeated immunofluorescence test could not be done because no frozen tissue was left, and no immunofluorescence test was done to the light chains. The result of IGA sediments along capillaries is not settled with subepithelial sediments in electron microscope (that were seen in only part of the capillaries).
 
February 2009
As a preparation for possible kidney transplant, an Ultrasound Doppler was preformed on the pelvic arteries. It demonstrated normal distal aorta, common iliac and external iliac – normal
 
March 2009
SPECT mapping of the heart – demonstrated normal LV systolic function. No signs of Ischemia. E Flt. Ventricle 63% (within normal).
 
Also attached are some more recent laboratory results.

Expert's Opinion

We do not know what the presenting symptoms were but the patient had a renal biopsy
done on January 2009. The diagnosis is that of chronic glomerulonephritis with
immune complex deposition. Some of the information we would like to have are not
reported (light chain, kappa and lamda light chain) but we do know that 5/18 glomeruli
are globally sclerosed. 13 had open capillaries and some of these have thickened
Bowman's capsule. 
 
We also know that the patient has: 
1. Stage 4-5 renal insufficiency 
2. Significant anemia 
3. Hyperparathyroidism
and the patient is on appropriate therapy for these conditions. 
 
Other Laboratory results include:
1. ASLO titre     445 IU/ml (0-200)  
2. Hep B and Hep C Negative
3. HIV Negative
4. ANA and lupus serologies Negative
5. Cryoglobulin (should be checked)
 
The cause of the immune complex deposition disease is unclear from the data
available. Possible causes include
1. Post-infectious glomerulonephritis (including post-strep glomerulonephritis, hepatitis B, hepatitis C and HIV); all are ruled out by the tests indicated although ASLO titer is indeed elevated
2. Lupus nephritis is ruled out with the negative ANA and negative serologies
3. Cryoglobulinemia is still a possibility
4. IgA nephropathy is still a consideration
5. Membranous nephropathy is less likely with the included information
6. Idiopathic immune complex mediated glomerulonephritis is obviously the diagnosis of
exclusion
 
The specific question that was asked was that of the timing of the transplant. The
interesting observation is that the patient's renal function appears to be getting better from the February data set to the March data set. Since patients with post-
infectious GN and inflammatory GN (such as lupus) can indeed improve after the acute flare, it would be prudent to continue to manage medically. Anti-hypertensive agents,Mimpara, Erythropoeitin and Venofen should be continued. Although the renal biopsy does show scaring with tubular atrophy and interstitial fibrosis, it is possible for the creatinine to settle in the 1.8 range. Over time, however, the renal function may
gradually progress to needing transplantation at a future date. 
 
With respect to transplantation:
1. It would be important to identify any potential donor since we do have time to
optimize this situation.
2. The patient should continue to try and optimize her body weight since steroid
administration after the transplant can significantly aggravate the weight issue.

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