Diabetic Nephropathy



The bright winter sun shines through the windows of your office as you prepare to see your first patient of the afternoon. You smile to yourself thinking of the warm spring and summer days to come. Before the consultation proper, you review a referral letter from your colleague, Dr. Hopkins, who works in the endocrinology department.


As per the letter, 60-year-old Mr. Geller has had type-2 diabetes mellitus for 20 years now, complicated by mild nonproliferative diabetic retinopathy. His medical history is significant for a left-sided ischemic stroke six years ago, without long-term complications. He is currently on metformin 2000 mg/day, gliclazide 80 mg/day, aspirin 100 mg/day, and atorvastatin 40 mg/day. Aside from some mild experimentation in his youth, he has not smoked. He does not consume alcohol now, and even earlier, only drank socially.


Dr. Hopkins requests that you evaluate Mr. Geller in the light of the following recent abnormal laboratory values: Creatinine: 2.24 mg/dL (0.7-1.3) Hemoglobin: 10.2 g/dL (14-17.5) Albumin: 2.8 g/dL (3.5-5.5) Urinalysis: 2+ proteinuria Two years ago, his annual lab values were within normal limits, except for microalbuminuria. He was supposed to have repeat labwork last year but was non-compliant.


As you enter the room, you encounter a jovial Mr. Geller who greets you with a handshake and a smile. "Good afternoon, Doctor," he states. "Good afternoon to you Mr. Geller! How are you feeling today?" you ask. "I am feeling fine, Doctor! This beautiful weather is a wonderful change from the rain we've been having," your patient remarks. "I'm enjoying the sunshine as well today, Mr. Geller. I've reviewed your referral letter, and Dr. Hopkins has asked me to evaluate you for some very serious issues," you say, as you get down to business.


"Mr. Geller, your lab work shows that you are anemic and that your kidneys are not functioning as well as they should. We need to do some further tests" you explain. "That is what Dr. Hopkins has already told me. I feel okay though and have been urinating fine," your patient states. Patients often confuse urinary output with renal function, so you take a moment to educate Mr. Gellar on the differences. "The kidneys are responsible for the excretion of many other elements besides water. Most of the time these abnormalities are only found on routine laboratory tests.", you say and continue, "Although you may be feeling just fine, your kidneys may not be properly removing these waste substances from your body. This could have serious long-term effects on your health."


Your words seem to have gotten Mr. Geller's attention, so you proceed with the consultation. On examination, his vitals are: BP 150/90 mmHg, pulse 73 bpm, temperature 36.8 ℃, and oxygen saturation 99% (on room air). Mr. Geller appears pale and has slight edema in both lower extremities. Ophthalmoscopy confirms the presence of mild nonproliferative diabetic retinopathy. The remainder of the examination is unremarkable.


"Mr. Geller, we need to perform several further tests to determine the best course of treatment," you explain. As you turn to your computer to enter the necessary requisitions, you notice that he seems uneasy. "Do you have any questions, Mr. Geller?" you ask. "Yes, Doctor. My endocrinologist told me to stop taking my tablets, and switch to insulin instead." "Do you think that this is really necessary? It seems very inconvenient", he adds.


You hand Mr. Geller the necessary lab requisitions and advise him to return in one week. He seems very pleased with your decision.


Mr. Geller seems to accept your recommendation, but you are worried that he may not fully understand the reason for discontinuing those medications. "You see, when the kidneys are not functioning properly, these drugs will build up in your system rather than being excreted out of the body. This can severely lower your blood sugar levels - potentially causing even death", you explain. Mr. Geller nods in understanding and agrees to get the necessary tests done.


Two days later, Mr. Geller is back in your clinic. His results are as follows: Hb: 9.3 g/dL (14-17.5 g/dL) RBC: 3.8x10^6 cells/mm3 (4.32-5.72) MCV: 78 fL (80-100) MCH: 24 pg (27-31) MCHC: 31 g/dL (32-36) Hct: 30% (38-50) Reticulocyte count: 1% (0.5-1.5) K+: 4.8 mmol/L (3.5-5) Na+: 137 mmol/L (135-145) Serum creatinine: 2.64 mg/dL (0.7-1.3) eGFR (EPI equation): 25 ml/min/1.73m2 (90-120) Urialysis: protein 2+; RBC negative. 24h proteinuria: 4130 mg/24h (<80) Renal ultrasound: no sign of ureteral obstruction, with normal renal sizes bilaterally. No features suggestive of renal artery stenosis. Fasting glucose: 137 mg/dL (75-100) 2h postprandial glucose: 248 mg/dL (<140) HbA1c: 7.8% (<7%) Serum ferritin: 84 ng/ml (23-336) Serum iron: 56 ug/dL (55-160) Serum transferrin saturation (TSAT): 15% (16-35) Total iron binding capacity (TIBC): 500 ug/dL (240-450) Serum vitamin B12: 356 pg/mL (200-900) Folate: 8 ng/mL (2.5-20) Total cholesterol: 140 mg/dL (<200) LDL cholesterol: 67 mg/dL (<70) HDL cholesterol: 45 mg/dL (40-50) Triglycerides: 138 mg/dL (<150) Ambulatory blood pressure monitoring: 24h average BP: 141/82 mmHg, HR 73 bpm Daytime (awake): 145/83 mmHg, HR 77 bpm Night-time (asleep): 137/78 mmHg, HR 68 bpm


Mr. Geller looks at you with shock on his face and asks, "WHAT?!!". You realize your mistake and quickly prevaricate, "my apologies - I meant to say that if you do not start taking care of your health, we might need to plan for hemodialysis at some point."


Drawing Mr. Geller's attention to the full blood count, you explain that his hemoglobin levels are low and that this needs to be addressed.


"Really?!?" Mr. Geller questions you with concern. You start to nod your head, but then suddenly realize that the lab results favor iron deficiency anemia.


"Your tests show that you have iron deficiency anemia, Mr. Geller. I want to start you on iron tablets immediately. I'm also pleased to tell you that you have good control of your lipid levels", you explain. "What about my blood pressure, Doctor?" Mr. Geller asks.


You proceed to start Mr. Geller on furosemide and arrange a follow-up visit in one month. However, several days later, you receive a phone call from Mr. Geller's wife who states that although his blood pressure has improved, she is worried the diuretic might be dehydrating him. After further research, you advise her that you will stop furosemide and start perindopril instead.


"Really? Dr. Hopkins seemed to think my blood pressure might be too high ..." Mr. Geller asks. You take a moment to review the most recent guidelines on the management of blood pressure in persons with diabetic nephropathy and find out that they recommend a pressure <140/90 mmHg. You proceed to prescribe perindopril and arrange a follow-up visit in one month.


A month later, Mr. Geller is back in your office. You've been keeping a close eye on his blood pressure, and the medication has been effective, without significant side effects. His latest blood pressure reading is 120/72 mmHg, while his most recent lab work reveals a Hb of 10.7 g/dL and Creatinine of 2.40 mg/dL.


A few days later, Mr. Geller's wife calls you. She sounds very worried, stating, "Doctor, I'm sorry to bother you, but my husband is not well. I thought that he might have eaten something bad because he's been vomiting and having diarrhea since yesterday. He is very fatigued and can't keep anything down, even water." You advise Mrs. Geller to bring her husband to the ER.


At the ER, you find Mr. Geller to be very dehydrated, with a blood pressure of 87/57 mmHg and a heart rate of 118 bpm. His temperature is 38.7 ℃. Examination of the abdomen reveals mild diffuse tenderness, without guarding or rebound tenderness. Bowel sounds are hyperactive. No other untoward examination findings are noted.


Urgent laboratory tests show the following: Hemoglobin: 13 g/dL (14-17.5) WBC: 13,740 cells/mm3 (3,500-10,500) Neutrophils: 85.7% (40-80) Random blood glucose: 100 mg/dL Creatinine: 4.47 mg/dL (0.7-1.3) Na+:141 mmol/L (135-145) K+: 4.9 mmol/L (3.5-5)


Mr. Geller's lab work and history suggest at acute kidney injury secondary to gastroenteritis. You admit him, stop perindopril, order stool and blood cultures, and commence intravenous antibiotics.


Your colleague who will be taking care of Mr. Geller in the inpatient ward disagrees stating, "This is most likely prerenal failure, which is very likely to reverse with adequate hydration. I suggest giving him intravenous fluids for now while monitoring his creatinine closely." Feeling somewhat embarrassed, you agree.


You decide to start Mr. Geller on intravenous fluids while monitoring his creatinine closely.


The following day, you check in to find that his condition has improved markedly. Mr. Geller's creatinine has gone back down to 2.72 mg/dL, and his blood pressure is stable at 122/74 mmHg. Subsequently, you restart perindopril and discharge him home with directions to be followed up every 3 months. As Mr. Geller and his wife thank you effusively and depart the hospital, you cannot help but feel a glow of satisfaction. Well done!


However, two days later, you receive a call from a very upset Dr. Hopkins. "Why did you tell Mr. Geller to not switch to insulin? He had an episode of hypoglycemia and fainted at home. Thank goodness his wife was there when it happened or else he could have died!" he exclaims. You feel awful as the gravity of your mistake sets in. Of course! Metformin and gliclazide accumulate when the eGFR is decreased. The buildup of these medications can subsequently cause severe hypoglycemia.